Glucocorticoid receptor [1,5,6]

- 对胶原蛋白合成的影响：在人类皮肤中，丁酸氢化可的松（局部应用）可抑制胶原蛋白合成。与氢化可的松相比，它显示出更强的抑制作用。局部应用后，14C-脯氨酸掺入皮肤胶原蛋白的量减少，表明胶原蛋白生成减少 [5]
- 血管收缩活性：在血管收缩试验中，局部应用丁酸氢化可的松（乳膏或软膏剂型）比氢化可的松表现出更强的血管收缩活性。血管收缩效果通过皮肤发白程度评估，丁酸氢化可的松可诱导更明显且持续时间更长的发白 [6]
- 在皮肤病中的临床疗效：丁酸氢化可的松（局部制剂）可有效治疗多种炎症性皮肤病，包括湿疹和皮炎。它能减轻这些疾病相关的发红、肿胀和瘙痒 [1]

- For vasoconstriction assay: Hydrocortisone butyrate is formulated into creams or ointments. These formulations are applied topically to the skin of human subjects (or animal models). The skin is observed at specific time points (e.g., 2, 4, 6, 24 hours) to assess the degree of blanching, which reflects vasoconstrictive activity. Comparisons are made with hydrocortisone formulations [6]
- For collagen synthesis study: Hydrocortisone butyrate is applied topically to human skin. After a specified period, 14C-proline is administered, and skin biopsies are taken. The incorporation of 14C-proline into collagen is measured to evaluate collagen synthesis inhibition [5]

Absorption, Distribution and Excretion
Topical corticosteroids can be absorbed from normal intact skin. Inflammation and/or other disease processes in the skin increase percutaneous absorption.
Corticosteroids are metabolized primarily in the liver and are then excreted by the kidneys. Some of the topical corticosteroids and their metabolites are also excreted into the bile.

---

Metabolism / Metabolites
Primarily hepatic via CYP3A4

---

Biological Half-Life
6-8 hours

- Allergic contact dermatitis: Topical application of Hydrocortisone butyrate can induce allergic contact dermatitis in some individuals, presenting as a papular eruption mimicking papular rosacea [8]
Protein Binding
95%

---

26133 rat LD50 oral >3 gm/kg Oyo Yakuri. Pharmacometrics., 8(991), 1974
26133 rat LD50 intraperitoneal >3 gm/kg BEHAVIORAL: CHANGES IN MOTOR ACTIVITY (SPECIFIC ASSAY); GASTROINTESTINAL: HYPERMOTILITY, DIARRHEA; KIDNEY, URETER, AND BLADDER: HEMATURIA Oyo Yakuri. Pharmacometrics., 8(991), 1974
26133 rat LD50 subcutaneous >3 gm/kg BEHAVIORAL: CHANGES IN MOTOR ACTIVITY (SPECIFIC ASSAY); GASTROINTESTINAL: HYPERMOTILITY, DIARRHEA; KIDNEY, URETER, AND BLADDER: HEMATURIA Oyo Yakuri. Pharmacometrics., 8(991), 1974
26133 mouse LD50 oral >3 gm/kg Oyo Yakuri. Pharmacometrics., 8(991), 1974
26133 mouse LD50 intraperitoneal 1550 mg/kg BEHAVIORAL: SOMNOLENCE (GENERAL DEPRESSED ACTIVITY); KIDNEY, URETER, AND BLADDER: HEMATURIA; SKIN AND APPENDAGES (SKIN): HAIR: OTHER Oyo Yakuri. Pharmacometrics., 8(991), 1974

[1]. Hydrocortisone 17-butyrate: a new topical corticosteroid preliminary report. Drugs, 1976, 12(4), 249–257.
[2]. Statistical design for formulation optimization of hydrocortisone butyrate-loaded PLGA nanoparticles. AAPS PharmSciTech. 2014 Jun;15(3):569-87.
[3]. Development of the hydrocortisone butyrate qualitative determination method. Ceska Slov Farm. Fall 2014;63(6):275.
[4]. Nanoparticle-Based Topical Ophthalmic Gel Formulation for Sustained Release of Hydrocortisone Butyrate. AAPS PharmSciTech. 2016 Apr;17(2):294-306.
[5]. Comparison of the effect of hydrocortisone, hydrocortisone-17-butyrate and betamethasone on collagen synthesis in human skin in vivo. Acta Derm Venereol. 1995 Jul;75(4):269-71.
[6]. Comparison of activity of different topical corticosteroid creams and ointments using a vasoconstriction assay: superiority of hydrocortisone butyrate over hydrocortisone]. J Dtsch Dermatol Ges. 2005 May;3(5):348-53.
[7]. Kinetics of decomposition and formulation of hydrocortisone butyrate in semiaqueous and gel systems. J Pharm Sci. 1983 Jul;72(7):776-81.
[8]. Allergic contact dermatitis induced by topical hydrocortisone-17-butyrate mimicking papular rosacea. Dermatitis. 2012 Mar-Apr;23(2):95-6.

- Hydrocortisone butyrate is a topical corticosteroid with higher potency than hydrocortisone. Its mechanism of action is mediated through binding to the glucocorticoid receptor, exerting anti-inflammatory, immunosuppressive, and antiproliferative effects [1,5,6]
- It is formulated into various topical preparations such as creams, ointments, and gels. Nanoparticle-based formulations (e.g., PLGA nanoparticles, ophthalmic gel) have been developed to improve its sustained release and targeted delivery [2,4]
- Stability studies show that Hydrocortisone butyrate can decompose in semiaqueous and gel systems, with factors like pH and temperature affecting its stability. Formulation optimization is needed to enhance its stability [7]
- A qualitative determination method for Hydrocortisone butyrate has been developed, which is used for quality control and identification of the drug in formulations [3]

---

Cortisol 17-butyrate is cortisol esterified with butyric acid at the 17-hydroxy group. It has a role as a dermatologic drug and a drug allergen. It is a cortisol ester, a butyrate ester and a primary alpha-hydroxy ketone.
Hydrocortisone Butyrate is the butyrate salt form of hydrocortisone, a synthetic glucocorticoid receptor agonist with antiinflammatory, antipruritic and vasoconstrictive effects. Binding and activation of the glucocorticoid receptor results in the activation of lipocortin that in turn inhibits cytosolic phospholipase A2. Lack of phospholipase A2 prevents the release of arachidonic acid, precursor for inflammatory mediator prostaglandins and leukotrienes, from the cell membrane. Secondly, mitogen-activated protein kinase (MAPK) phosphatase 1 is induced, thereby leading to dephosphorylation and inactivation of Jun N-terminal kinase directly inhibiting c-Jun mediated transcription. Finally, transcriptional activity of nuclear factor (NF)-kappa-B is blocked, thereby inhibits the transcription of cyclooxygenase 2, which is essential for prostaglandin production.

---

Drug Indication
For the relief of the inflammatory and pruritic manifestations of corticosteroid-responsive dermatoses. Also used to treat endocrine (hormonal) disorders (adrenal insufficiency, Addisons disease). It is also used to treat many immune and allergic disorders, such as arthritis, lupus, severe psoriasis, severe asthma, ulcerative colitis, and Crohn's disease.

---

Mechanism of Action
Hydrocortisone binds to the cytosolic glucocorticoid receptor. After binding the receptor the newly formed receptor-ligand complex translocates itself into the cell nucleus, where it binds to many glucocorticoid response elements (GRE) in the promoter region of the target genes. The DNA bound receptor then interacts with basic transcription factors, causing the increase in expression of specific target genes. The anti-inflammatory actions of corticosteroids are thought to involve lipocortins, phospholipase A2 inhibitory proteins which, through inhibition arachidonic acid, control the biosynthesis of prostaglandins and leukotrienes. Specifically glucocorticoids induce lipocortin-1 (annexin-1) synthesis, which then binds to cell membranes preventing the phospholipase A2 from coming into contact with its substrate arachidonic acid. This leads to diminished eicosanoid production. The cyclooxygenase (both COX-1 and COX-2) expression is also suppressed, potentiating the effect. In other words, the two main products in inflammation Prostaglandins and Leukotrienes are inhibited by the action of Glucocorticoids. Glucocorticoids also stimulate the lipocortin-1 escaping to the extracellular space, where it binds to the leukocyte membrane receptors and inhibits various inflammatory events: epithelial adhesion, emigration, chemotaxis, phagocytosis, respiratory burst and the release of various inflammatory mediators (lysosomal enzymes, cytokines, tissue plasminogen activator, chemokines etc.) from neutrophils, macrophages and mastocytes. Additionally the immune system is suppressed by corticosteroids due to a decrease in the function of the lymphatic system, a reduction in immunoglobulin and complement concentrations, the precipitation of lymphocytopenia, and interference with antigen-antibody binding.

C25H36O6

432.55

432.251

C, 69.42; H, 8.39; O, 22.19

13609-67-1

Hydrocortisone acetate; 50-03-3; Hydrocortisone; 50-23-7; Hydrocortisone phosphate; 3863-59-0

26133

White to off-white solid powder

1.2±0.1 g/cm3

585.6±50.0 °C at 760 mmHg

212 °C

194.0±23.6 °C

0.0±3.7 mmHg at 25°C

1.565

2.81

100.9

2

6

6

31

817

7

C[C@@]12[C@](C(CO)=O)(OC(CCC)=O)CC[C@@]1([H])[C@]3([H])CCC4=CC(CC[C@]4(C)[C@@]3([H])[C@@H](O)C2)=O

BMCQMVFGOVHVNG-TUFAYURCSA-N

InChI=1S/C25H36O6/c1-4-5-21(30)31-25(20(29)14-26)11-9-18-17-7-6-15-12-16(27)8-10-23(15,2)22(17)19(28)13-24(18,25)3/h12,17-19,22,26,28H,4-11,13-14H2,1-3H3/t17-,18-,19-,22+,23-,24-,25-/m0/s1

[(8S,9S,10R,11S,13S,14S,17R)-11-hydroxy-17-(2-hydroxyacetyl)-10,13-dimethyl-3-oxo-2,6,7,8,9,11,12,14,15,16-decahydro-1H-cyclopenta[a]phenanthren-17-yl] butanoate

H.17B; Locoid; Alfason; hydrocortisone butyrate; Hydrocortisone 17-butyrate; Cortisol 17-butyrate; Hydrocortisone-17-butyrate; 13609-67-1; Locoid; Hydrocortisone-17alpha-butyrate; Locoid Lipocream; Hydrocortisone butyrate; Hydrocortisone 17-butyrate; Locoid lipocream

2934.99.03.00

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

DMSO: ~87 mg/mL (~201.1 mM)
Ethanol: ~15 mg/mL

配方 1 中的溶解度: ≥ 2.08 mg/mL (4.81 mM) (饱和度未知) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液。
例如，若需制备1 mL的工作液，可将100 μL 20.8 mg/mL澄清DMSO储备液加入400 μL PEG300中，混匀；然后向上述溶液中加入50 μL Tween-80，混匀；加入450 μL生理盐水定容至1 mL。
*生理盐水的制备：将 0.9 g 氯化钠溶解在 100 mL ddH₂O中，得到澄清溶液。

---

配方 2 中的溶解度: ≥ 2.08 mg/mL (4.81 mM) (饱和度未知) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液。
例如，若需制备1 mL的工作液，可将 100 μL 20.8 mg/mL澄清DMSO储备液加入900 μL 20% SBE-β-CD生理盐水溶液中，混匀。
*20% SBE-β-CD 生理盐水溶液的制备（4°C，1 周）：将 2 g SBE-β-CD 溶解于 10 mL 生理盐水中，得到澄清溶液。

---

View More

配方 3 中的溶解度: ≥ 2.08 mg/mL (4.81 mM) (饱和度未知) in 10% DMSO + 90% Corn Oil (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液。
例如，若需制备1 mL的工作液，可将 100 μL 20.8 mg/mL 澄清 DMSO 储备液加入到 900 μL 玉米油中并混合均匀。

---

请根据您的实验动物和给药方式选择适当的溶解配方/方案：
1、请先配制澄清的储备液(如：用DMSO配置50 或 100 mg/mL母液(储备液));
2、取适量母液，按从左到右的顺序依次添加助溶剂，澄清后再加入下一助溶剂。以 下列配方为例说明 (注意此配方只用于说明，并不一定代表此产品 的实际溶解配方):
10% DMSO → 40% PEG300 → 5% Tween-80 → 45% ddH2O (或 saline);
假设最终工作液的体积为 1 mL, 浓度为5 mg/mL: 取 100 μL 50 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀/澄清；向上述体系中加入50 μL Tween-80，混合均匀/澄清；然后继续加入450 μL ddH2O (或 saline)定容至 1 mL；
3、溶剂前显示的百分比是指该溶剂在最终溶液/工作液中的体积所占比例;
4、 如产品在配制过程中出现沉淀/析出，可通过加热(≤50℃)或超声的方式助溶;
5、为保证最佳实验结果，工作液请现配现用！
6、如不确定怎么将母液配置成体内动物实验的工作液，请查看说明书或联系我们;
7、 以上所有助溶剂都可在 Invivochem.cn网站购买。