HYDROXYETHYLCELLULOSE
化妆品中 羟乙基纤维素 (HYDROXYETHYLCELLULOSE) 的全球法规限值与配方应用标准是什么?
羟乙基纤维素(标准 INCI: HYDROXYETHYLCELLULOSE,CAS 号: 9004-62-0)是化妆品配方中主要用作成膜剂, 粘度调节剂, 粘合剂的核心成分。受中国 NMPA(已使用/准用)、韩国 MFDS(未列管)及欧盟 CosIng(未列管)等 6 大法域法定标准监管,常规建议添加量为 0.15–1.5%(最佳稳定窗口 pH 2–10)。
全球 7 轨官方全成分标签名称对照表
严格采用各国政府官方目录原名 · 严禁机器翻译| 法域与监管轨道 | 官方公告全成分标准名称 | 一键复制 |
|---|---|---|
| ① 韩国 (MFDS 化妆品标准名称) | HYDROXYETHYLCELLULOSE (KR MFDS Registered) | |
| ② 韩国旧名称历史 (301 重定向) | Former KR Nomenclature Redirect Active | — |
| ③ 欧盟 (EU CosIng EC 1223/2009) | HYDROXYETHYLCELLULOSE | |
| ④ 美国普通化妆品 (US PCPC / MoCRA INCI) | HYDROXYETHYLCELLULOSE | |
| ⑤ 美国 OTC 防晒/祛痘专论活性物名称 (FDA OTC) | — (非美国 OTC 专论活性成分 / 普通化妆品原料) | — |
| ⑥ 中国 (NMPA《已使用化妆品原料目录 IECIC》标准中文名) | 羟乙基纤维素 | |
| ⑦ 日本普通化妆品 / 医药部外品 (JCIA / MHLW) | ヒドロキシエチルセルロース · [QD: ヒドロキシエチルセルロース] |
Layer 1 — 全球 6 大法域法定限值与监管状态
| 法域 | 监管状态 | 法定限值 | 适用条件与法定依据来源 |
|---|---|---|---|
| 韩国 (MFDS) | 未列管 | GMP | 已列入官方化妆品原料目录 (按 GMP 规范使用) |
| 欧盟 (EU) | 未列管 | GMP | 已列入官方化妆品原料目录 (按 GMP 规范使用) |
| 美国 (FDA) | 未列管 | GMP | 已列入官方化妆品原料目录 (按 GMP 规范使用) |
| 中国 (NMPA) | 已使用/准用 | GMP | IECIC Entry #5294 |
| 日本 (MHLW) | 未列管 | GMP | 已列入官方化妆品原料目录 (按 GMP 规范使用) |
| 东盟 (ACD) | 未列管 | GMP | 已列入官方化妆品原料目录 (按 GMP 规范使用) |
Layer 2 — 毒理评估与历史最高使用量 (CN IECIC / US CIR / EU SCCS)
“欧盟 SCCS 安全评估上限”代表消费者安全科学委员会判定安全边际 (MoS≥100) 的毒理阈值;“美国 CIR 市售最高报告浓度”与“中国 IECIC 最高历史使用量”代表已上市化妆品的最高实际使用浓度。
| 安全评估依据 | 适用范围与剂型 | 评估浓度范围 | 评估结论与文献档案 |
|---|---|---|---|
| 中国 IECIC 最高历史使用量 | leave_on | ≤ 3% | 安全判定 (MoS≥100)NMPA IECIC (2025) Entry 05348 (2025) |
| 中国 IECIC 最高历史使用量 | rinse_off | ≤ 3% | 安全判定 (MoS≥100)NMPA IECIC (2025) Entry 05348 (2025) |
Layer 3 Formulation Concentration Box-Plot vs. Statutory Limit
Layer 3 — 剂型常规配比指南与理化配伍性
| 剂型分类 | Min – Q1 – Median – Q3 – Max (%) | 配方作用与机理 | Source ID |
|---|---|---|---|
| 剂型组 A — 水剂爽肤水 / 精华液 / 安瓶 | 0.15% · 0.3% · 0.5% · 0.8% · 1.5% | Non-ionic clear aqueous serum & sheet-mask thickener | Ashland Natrosol 250HHR TDS & CIR Assessment |
| 剂型组 B — 乳液 / 面霜 (O/W · W/O) | 0.2% · 0.375% · 0.5% · 0.7125% · 1% | Emulsion cream & lotion structural / conditioning agent | Global Starter Formulation Library Statistical Distribution (n=12, EVONIK 8 · GRANT 4) |
Stratum Corneum Penetration Depth & Bio-Spicule Transdermal Delivery
Under passive topical application, molecules diffuse tortuously through intercellular lipids. Hydrophilic compounds >500 Da remain primarily on the outer stratum corneum.
pH Stability Window (0–14), Thermal Limit & HLB Colloidal Phase Behavior
Outside pH 2–10, risk of hydrolysis, viscosity loss, or ionic dissociation increases.
Thermally stable up to 85°C during standard emulsification.
Cellular & Molecular Target Mechanism Flow
Interactive Synergy Pairings (Solid) & Incompatibility Warnings (Dashed)
Click any green synergy node to jump directly to its monograph, or click a red dashed node to inspect the chemical incompatibility mechanism.
商品名仅供配方师识别原料规格参考,商标权归各原厂商所有。
学术与毒理综合摘要
Tier 1 Synthesis本综述严格基于与该原料关联的 NIH PubMed 同行评审文献摘要及官方毒理学评估档案编写。
关联同行评审文献 (NIH PubMed) (12)
Hydroxyethyl cellulose as carbohydrate polymer scaffold for surfactant-free serums with enhanced hydration and structural stability [PMID: 42214523 · 2026]
Conventional cosmetic serums often suffer from rapid dehydration, phase separation, and component aggregation, leading to non-uniform ingredient dispersion and limited hydration durability. In this study, hydroxyethyl cellulose (HEC) was investigated as a structural modifier to improve the physicochemical stability and moisturizing performance of surfactant-free cosmetic serums. Moisture retention tests showed that HEC-containing formulations exhibited improved hydration durability, with moisture loss limited to approximately 5% after 30 min even after 7 days of storage. Extended measurements further showed that HEC-containing systems maintained higher moisture retention over longer time scales than HEC-free formulations. Scanning electron microscopy revealed a smoother and more homogeneous dried microstructure in the presence of HEC, indicating improved structural uniformity without conventional surfactants. Thermogravimetric analysis showed altered dehydration behavior, suggesting modified water-binding environments rather than changes in intrinsic thermal stability. FT-IR spectroscopy with peak deconvolution provided strong evidence for intermolecular hydrogen bonding between the hydroxyl groups of HEC and the carbonyl groups of sodium hyaluronate, while complementary 1 H NMR analysis revealed peak broadening and subtle chemical shift variations, indicating changes in local proton environments and intermolecular interactions. These results support the formation of a stabilized polymeric network by HEC, which contributes to improved structural integrity and sustained hydration performance in surfactant-free serum systems.
A simple and effective hydrogel dressing for advanced management of full-thickness skin wound by multi-functional strategies [PMID: 41299619 · 2025]
In clinical practice, wound treatment continues to be a significant concern. The wound healing process is intricate and continuous. Hemostasis is the initial stage and the primary variables influencing wound healing include bacterial infection and oxidative stress. To tackle these issues, a novel hydrogel dressing was constructed, composed of chitosan hydrochloride (CSCl), hydroxyethyl cellulose (HEC), glucose and resveratrol nanoemulsion (RES-NE). The innovative RES-NE loaded chitosan hydrogel (RN-CH) features controllable gelation time, rapid self-healing property, appropriate injectability, and strong tissue adhesion ability. Additionally, it exhibits excellent biocompatibility, antioxidant property, antibacterial activity, and significant hemostasis capability. Pharmacodynamic experiments reveal that RN-CH can effectively promote full-thickness wounds healing by modulating inflammation, mitigating oxidative stress, and facilitating early angiogenesis and collagen formation.
The Structural Design and Experimental Analysis of a Microneedle with Microchannels: Capable of Achieving Ultrafast Body Fluid Extraction [PMID: 41105561 · 2025]
In this study, microneedles (MNs) arrays with microchannels were prepared based on poly(vinyl alcohol) and hydroxyethylcellulose composite materials. The finite element method was adopted to optimize the size of microchannels and the needle tip by establishing the skin penetration model and the human interstitium fluid (ISF) extraction model. The results show that they are positively correlated with the stress during skin penetration. The extraction rate of ISF varies as a function of the microchannel size, initially increasing and then decreasing (with the peak extraction speed occurring at a diameter of 10 μm). Comprehensively considering the manufacture and structural strength, the MNs array with the extremely fast ISF extraction (45.0 ± 2.1 s) and excellent skin penetration ability was prepared (with the microchannel diameter of 4 μm and the needle tip diameter of 10 μm). Furthermore, the microchannel of MNs arrays prepared with soluble materials can continuously increase with the extraction of ISF, enabling it to have a faster extraction speed of ISF while also demonstrating the excellent skin penetration ability. This has halved the time for the MNs sensor to complete the detection. This work lays the foundation for the development of efficient ISF acquisition and the realization of in situ ISF detection technology.
Liposomes containing sorbitan monolaurate incorporated in hydroxyethylcellulose hydrogels for topical delivery of 5-fluorouracil: rheological characterization, skin penetration and cytotoxicity study [PMID: 40494416 · 2025]
In this work, liposomes composed of soy phosphatidylcholine (SPC) and cholesterol (CHOL), in addition to sorbitan monolaurate (span 20), a skin penetration enhancer, were incorporated into hydroxyethylcellulose (HEC) hydrogels to optimize the topical administration of 5-fluorouracil (5-FU) employed in treatment of skin cancer. The formulations were stable (pH, density, viscosity) in the period of 30 days. Furthermore, the pseudoplastic behavior with thixotropy of the developed hydrogels, in the presence or absence of liposomes, was confirmed, proving that liposome incorporation does not compromise their rheological characteristics, maintaining desirable aspects for topical application. Texture and bioadhesion studies also demonstrated the ability of hydrogels associated with liposomes to present good spreadability in parallel with increased contact time of the drug on the skin. Although it was not possible to quantify the active ingredient from the hydrogels, the in vitro release test allowed us to observe a prolonged release of 5-FU by the nanocarriers, which, associated with the polymeric matrix, suggests a system capable of protecting the drug from the physiological environment, while providing effective delivery. Liposomes containing span 20, incorporated into the HEC hydrogel, were capable of delivering 1194,8 ng/cm 2 of 5-FU into viable epidermis + dermis, observed in the in vitro skin penetration study, unlike samples containing liposomes without span, in which it was not possible to quantify the drug in the skin layers. Therefore, not only we were able to show the potential of span 20 to promote drug skin penetration, but we also proved that with the incorporation of liposomal dispersions in HEC hydrogels, fundamental for enabling their topical application, this property is maintained. Finally, in vitro cytotoxicity evaluated in the A431 cell line provided IC 50 values of 1.953 μM, corroborating that hydrogels containing span 20 liposomes containing 5-FU are indeed a promising strategy for potential treatment of skin cancer.
Adsorption and Bulk Assembly of Quaternized Hydroxyethylcellulose-Anionic Surfactant Complexes on Negatively Charged Substrates [PMID: 39861278 · 2025]
This study examines the adsorption and bulk assembly behaviour of quaternized hydroxyethylcellulose ethoxylate (QHECE)-sodium dodecyl sulphate (SDS) complexes on negatively charged substrates. Due to its quaternized structure, QHECE, which is used in several industries, including cosmetics, exhibits enhanced electrostatic interactions. The phase behaviour and adsorption mechanisms of QHECE-SDS complexes are investigated using model substrates that mimic the wettability and surface charge of damaged hair fibres. Two preparation methodologies, high-concentration mixing and gradient-free mixing , were employed to examine their impact on the complex equilibrium, phase behaviour, and adsorption properties of the complexes. The measurements of turbidity, electrophoretic mobility, and conductivity demonstrate the existence of nonequilibrium dynamics during the mixing process, which exert a significant influence on the structural and functional characteristics of the complexes. The quartz crystal microbalance with dissipation monitoring (QCM-D) was employed to investigate the adsorption of the complexes onto the substrates. The results demonstrated the critical role of intermediate SDS concentrations in enhancing deposition. The findings emphasise the importance of formulation and preparation protocols in designing stable, high-performance cosmetic products. This research advances our understanding of polyelectrolyte-surfactant interactions and provides insights into optimising QHECE-based formulations.
The Wound-Healing Effect of a Novel Fibroblasts-Impregnated Hydroxyethylcellulose Gel in a Rat Full-Thickness Burn Model: A Preclinical Study [PMID: 39457528 · 2024]
Background/Objectives: The objective of this study was to assess the efficacy of a cell-containing wound dressing based on fibroblasts in hydroxyethylcellulose (HEC) gel for the local treatment of deep partial-thickness and/or full-thickness skin burns in an animal model. Methods: The rats (male Wistar, n = 100) were subjected to a full-thickness thermal burn (16 cm 2 ). Radical necrectomy was performed one day after the burn. Three days later, the rats were randomly assigned to one of four groups: group 1 (no treatment), group 2 (chloramphenicol and methyluracil ointment, a routine clinical treatment), group 3 (a gel without cells, mock treatment), and group 4 (a dermal fibroblast-impregnated HEC gel). The treatment lasted for five days. The wound-healing process was evaluated by planimetric, cytologic, histologic, and immunohistochemical methods. Results: The differences in the rate of wound healing and the characteristics of wound cytology were identified. In the group 4, a regenerative type of cytogram was revealed, characterized by a significantly increased number of fibroblastic cells in comparison to samples from non-treated and mock-treated animals. Biopsy samples of burn wounds from animals in the group 4l demonstrated the presence of mature granulation tissue and a large number of microvessels. The repair process was stimulated, as evidenced by the increased thickness of newly formed granulation tissue and epidermis in the wound zone, elevated cellularity, and enhanced re-epithelialization activity. The number of Ki-67-positive proliferating cells was significantly higher in group 4 than in the control groups). A small number of non-proliferating donor fibroblasts was observed in the wound area 3 days after the end of treatment. Conclusions: The cell product is an effective agent for promoting wound healing during the regenerative phase. The experiments demonstrated that a gel populated by dermal fibroblasts can stimulate reparative regeneration processes in deep partial- and full-thickness burn wounds.
Multifunctional hybrid lipid-polymeric nanoparticle enabling resveratrol and siRNA co-delivery for enhanced cutaneous wound repair [PMID: 42177899 · 2026]
Chronic ulcers impose a significant global healthcare burden due to the limited availability of effective and durable treatments. Impaired spatial and temporal coordination of immune, epithelial, and endothelial responses contributes to persistent inflammation and defective tissue repair. To address this complexity, in this study, we report the rational design and characterization of a hybrid lipid-polymeric nanoparticle (HLPN) platform for prolonged topical co-delivery of resveratrol (RSV), targeting oxidative and inflammatory pathways, and siRNA against matrix metalloproteinase-9 (siMMP9), a key mediator of chronicity. The optimized HLPNs exhibited a mean diameter of ∼180 nm, low polydispersity (PDI <0.2), and positive surface charge (∼20 mV), with high RSV encapsulation efficiency (98%). Surface-complexed siRNA remained protected from RNase degradation for up to 24 h. Incorporation of HLPNs into a hydroxyethylcellulose hydrogel resulted in favorable colloidal properties, leading to enhanced penetration and retention of the therapeutic agents in both intact and barrier-impaired skin. HLPN effectively mediated the cellular uptake of siRNA, resulting in significant MMP-9 gene silencing (≈11-36.5-fold reduction). The co-delivery system also markedly decreased intracellular reactive oxygen species and pro-inflammatory cytokines TNF-α and IL-6 (≈3.8 and 12.9-fold). Importantly, lipopolysaccharide-induced impairment of fibroblast migration was reversed, with the HLPN-RSV-siMMP9 formulation increasing cell migration compared with untreated inflamed controls. Together, these findings demonstrate that the multifunctional HLPN platform developed enables effective multimodal modulation of inflammatory and proteolytic pathways, representing a promising nanotherapeutic strategy for chronic wound management.
Development, Stability, and Clinical Efficacy of an Oil-in-Serum Formulation with Olive Extract Standardized in Hydroxytyrosol for Post-Inflammatory Hyperpigmentation Treatment [PMID: 41507660 · 2026]
Post-inflammatory hyperpigmentation (PIH) is a prevalent dermatological condition arising from inflammatory processes that significantly impacts quality of life. Natural alternatives to conventional treatments are increasingly sought to minimize adverse effects while maintaining efficacy. This study aimed to develop and evaluate an innovative oil-in-serum formulation containing olive extract standardized in hydroxytyrosol (HT) for PIH treatment, assessing its stability, sensory properties, and clinical efficacy. Two complementary formulations were developed: a hydroxyethylcellulose-based gel (with/without 0.1% olive extract containing 20% HT) and an olive oil-based formulation. Stability tests, texture analysis, sensory evaluation and clinical efficacy analysis in participants with PIH were conducted. Overall, the formulations were stable and showed favorable sensory properties. The oil-in-serum system exhibited enhanced spreadability, hydration perception, and reduced stickiness compared to individual components. After 45 days of application, the formulation with HT increased stratum corneum water content and reduced transepidermal water loss (TEWL), indicating improved skin barrier function. A significant reduction in color difference between lesional and perilesional areas was observed in high-resolution imaging analysis, showing a reduction in the PIH. Participants reported enhanced skin hydration and reduced dark spots, which corroborate the instrumental measurements results. Finally, the oil-in-serum formulation with olive extract standardized in HT proved effective for PIH treatment, combining excellent sensory properties with clinical efficacy in improving skin hydration, barrier function, and hyperpigmentation control.
Colloidal stability and controlled release of Au@SiO₂ and Ag@SiO₂ core-shell nanostructures from biopolymer-based hydrogels [PMID: 41366278 · 2025]
Nanotechnology offers innovative strategies for developing multifunctional cosmetic ingredients. Here, we synthesize Au@SiO₂ and Ag@SiO₂ core-shell nanostructures with high shape and size uniformity, colloidal stability, and hydrophilicity. The silica shell stabilizes the metal core and enables surface functionalization, enhancing applicability in biopolymer-based formulations. We characterize the nanomaterials using UV-Vis spectroscopy, TEM, DLS, zeta potential, and contact angle measurements, confirming well-defined core-shell morphology and favorable surface properties. Both nanostructures display comparable antioxidant activity, while Ag@SiO₂ exhibits superior catalytic efficiency. To evaluate delivery performance, we incorporate the nanoparticles into sodium hyaluronate (HA) and hydroxyethylcellulose (HEC) hydrogels. The hybrid gels maintain homogenous morphology and enable tunable nanoparticle release profiles: HA gels promote rapid release and significantly improve skin hydration, whereas HEC gels provide sustained release suitable for prolonged action. These results demonstrate that Au@SiO₂ and Ag@SiO₂ nanostructures act as versatile, stable, and bioactive components for cosmetic and biomedical formulations. The study highlights the potential of core-shell nanomaterials at soft matter interfaces, combining antioxidant and antimicrobial functionality with controlled delivery and enhanced skin barrier performance.
Evaluation of smart bi-functional dressing based on polysaccharide hydrogels and Brassica oleracea extract for wound healing and continuous monitoring [PMID: 39638175 · 2025]
Skin wounds can drive global impacts, socially and economically, in parallel with their elevated incidence rate. Therefore, utilizing the dual-activity of Brassica Oleracea (Red Cabbage) extract, of being pH-sensitive and biologically active in designing novel, therapeutic, and pH-sensitive wound dressings with an easily stripped-off feature, is critical. Wound dressings were designed using two separate hydrogels based on chitosan (CS) and hydroxyethylcellulose (HEC), each loaded with RCE. The pH sensitivity of prepared bandages exhibited a noticeable visual change in color during wound treatment. Wound closure has reached 99.69 % for CS/RCE dressings. Results showed that RCE had raised the hydroxyproline and collagen content in the healed skin. Histopathological investigation proves that skin returned to its regular thickness within 10 days of treatment. RCE showed marked improvement in the healing quality by acting as an antioxidant, anti-inflammatory, and antimicrobial agent. Therefore, dual-function dressings are potential candidates to sense and cure skin wounds.
Insulin-Loaded Chitosan-Cellulose-Derivative Hydrogels: In Vitro Permeation of Hormone through Strat-M(®) Membrane and Rheological and Textural Analysis [PMID: 39339083 · 2024]
This work is part of the current research trend to develop a hydrogel carrier of insulin to promote wound healing. Topically applied insulin promotes keratinocyte proliferation and migration, increases collagen synthesis, reduces inflammation and oxidative stress, and exhibits antimicrobial activity. The aim of this study was to design an insulin hydrogel matrix based on selected cellulose derivatives (methylcellulose, hydroxyethylcellulose, and hydroxypropylmethylcellulose) and chitosan. Rheological parameters of the formulations were evaluated using rotational rheometry and an oscillation test. Textural tests were performed. In vitro pharmaceutical insulin availability studies were carried out using the innovative Strat-M ® membrane to imitate the skin barrier. It was found that the pharmaceutical formulation of insulin based on chitosan and methylcellulose showed an acceptable balance between rheological and textural parameters and ease of application. The API was released from the carrier in a prolonged manner, eliminating the need to apply the formulation several times per day. The developed hydrogel shows potential for use in clinical practice.
Development of novel antimicrobials with engineered endolysin LysECD7-SMAP to combat Gram-negative bacterial infections [PMID: 39044206 · 2024]
Among the non-traditional antibacterial agents in development, only a few targets critical Gram-negative bacteria such as carbapenem-resistant Pseudomonas aeruginosa, Acinetobacter baumannii or cephalosporin-resistant Enterobacteriaceae. Endolysins and their genetically modified versions meet the World Health Organization criteria for innovation, have a novel mode of antibacterial action, no known bacterial cross-resistance, and are being intensively studied for application against Gram-negative pathogens. The study presents a multidisciplinary approach, including genetic engineering of LysECD7-SMAP and production of recombinant endolysin, its analysis by crystal structure solution following molecular dynamics simulations and evaluation of antibacterial properties. Two types of antimicrobial dosage forms were formulated, resulting in lyophilized powder for injection and hydroxyethylcellulose gel for topical administration. Their efficacy was estimated in the treatment of sepsis, and pneumonia models in BALB/c mice, diabetes-associated wound infection in the leptin receptor-deficient db/db mice and infected burn wounds in rats. In this work, we investigate the application strategies of the engineered endolysin LysECD7-SMAP and its dosage forms evaluated in preclinical studies. The catalytic domain of the enzyme shares the conserved structure of endopeptidases containing a putative antimicrobial peptide at the C-terminus of polypeptide chain. The activity of endolysins has been demonstrated against a range of pathogens, such as Klebsiella pneumoniae, A. baumannii, P. aeruginosa, Staphylococcus haemolyticus, Achromobacter spp, Burkholderia cepacia complex and Haemophylus influenzae, including those with multidrug resistance. The efficacy of candidate dosage forms has been confirmed in in vivo studies. Some aspects of the interaction of LysECD7-SMAP with cell wall molecular targets are also discussed. Our studies demonstrate the potential of LysECD7-SMAP therapeutics for the systemic or topical treatment of infectious diseases caused by susceptible Gram-negative bacterial species and are critical to proceed LysECD7-SMAP-based antimicrobials trials to advanced stages.
常见问题解答 (FAQ)
- Q1. 羟乙基纤维素 (HYDROXYETHYLCELLULOSE) 在全球 7 大法域的官方全成分标签名称是什么?
- 中国 NMPA《已使用化妆品原料目录 (IECIC)》标准中文名为 '羟乙基纤维素',美国 PCPC 与欧盟 CosIng 标准 INCI 为 'HYDROXYETHYLCELLULOSE',日本 JCIA 表示名称为 'ヒドロキシエチルセルロース'。
- Q2. 羟乙基纤维素 (HYDROXYETHYLCELLULOSE) 在中、韩、欧、美、日、东盟的法定监管状态 (Layer 1) 如何?
- 6 大法域监管汇总 — 中国(CN): allowed,韩国(KR): none,欧盟(EU): none,美国(US): none,日本(JP): none,东盟(ASEAN): none。
- Q3. 羟乙基纤维素 (HYDROXYETHYLCELLULOSE) 的常规配方添加量 (Layer 3) 与最佳稳定 pH 窗口是多少?
- 在代表性剂型 (aqueous_serum) 中常规添加量为 0.15%–1.5%(中位数 0.5%),最佳稳定 pH 范围为 2–10。
- Q4. 羟乙基纤维素 (HYDROXYETHYLCELLULOSE) 有哪些配伍禁忌 (Incompatibilities) 与协同增效组合?
- 推荐协同组合包括 COPPER TRIPEPTIDE-1, BEHENTRIMONIUM CHLORIDE, ZINC PCA;配伍禁忌注意:100% compatible with cationics and metal ions (GHK-Cu); high levels (>0.8%) may cause film rolling upon drying。