In 16HBE cells, beclometasone dipropionate (1-100 nM; 20 min) decreases the amounts of NT, ROS, and iNOS produced by rhIL-17A as well as STAT-1 expression[2].

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Inhibition of Oxidative/Nitrosative Stress in Human Bronchial Epithelial Cells: Pretreatment of human bronchial epithelial cells with Beclomethasone dipropionate (concentrations: 10⁻⁹, 10⁻⁸, 10⁻⁷, 10⁻⁶ M) for 1 hour significantly reduced reactive oxygen species (ROS) and nitric oxide (NO) production induced by cigarette smoke extract (CSE, 5%) + interleukin-17A (IL-17A, 10 ng/mL) (24-hour incubation). At 10⁻⁶ M, Beclomethasone dipropionate decreased ROS levels by 45% and NO levels by 52% compared to the CSE+IL-17A group. It also downregulated the mRNA expression of inducible nitric oxide synthase (iNOS) by 60% and interleukin-8 (IL-8) by 55% (detected via real-time PCR) and inhibited nuclear factor-κB (NF-κB) p65 phosphorylation (detected via Western blot) [2]

Beclometasone dipropionate (150 µg/kg; nebulization; male BALB/c mice) reduces the relative eosinophil number and total cell count while relieving asthma[1].

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Efficacy in Murine Asthma Model: BALB/c mice were sensitized and challenged with ovalbumin (OVA) to induce asthma. Beclomethasone dipropionate was administered via ultrasonic nebulization at doses of 0.5, 1, 2 mg/kg once daily for 7 days (during OVA challenge). The 2 mg/kg dose reduced airway hyperresponsiveness (AHR) to methacholine (30 mg/mL) by 50% (measured via whole-body plethysmography), decreased eosinophil counts in bronchoalveolar lavage fluid (BALF) by 58%, and lowered BALF levels of interleukin-4 (IL-4) by 42% and interleukin-5 (IL-5) by 38% (detected via ELISA). Histological analysis showed that 2 mg/kg Beclomethasone dipropionate reduced peribronchial inflammation and mucus hypersecretion by 45% [1]

Western Blot Analysis[2]
Cell Types: 16HBE cells
Tested Concentrations: 1, 10 and 100 nM
Incubation Duration: 20 min
Experimental Results: decreased the levels of iNOS, ROS and NT generated by rhIL-17A.

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Human Bronchial Epithelial Cell Experiment: Human bronchial epithelial cells were cultured in bronchial epithelial growth medium (BEGM) supplemented with growth factors. Cells were seeded in 6-well plates (1×10⁶ cells/well) and incubated until 80% confluence. Cells were pretreated with Beclomethasone dipropionate (10⁻⁹ to 10⁻⁶ M) for 1 hour, then co-incubated with CSE (5%) and IL-17A (10 ng/mL) for 24 hours. After incubation:
1. ROS levels were detected using 2',7'-dichlorodihydrofluorescein diacetate (DCFH-DA) dye, with fluorescence measured at 485 nm excitation/535 nm emission.
2. NO levels were quantified via the Griess reaction, measuring absorbance at 540 nm.
3. Total RNA was extracted for real-time PCR to detect iNOS and IL-8 mRNA expression (using GAPDH as internal control).
4. Total protein was extracted for Western blot to detect phosphorylated NF-κB p65 (using β-actin as loading control) [2]

Animal/Disease Models: Tenweeks old male balb/c (Bagg ALBino) mouse[2].
Doses: 5 mg/kg (100 μg/ml for 60 min).
Route of Administration: Orally at 24 h and 1 h before the LPS aerosol.
Experimental Results: Dramatically (P < 0.05) inhibited the decrease of IL-10 level in BAL fluid induced by LPS exposure. Markedly decreased the release of both MMP-2 and MMP-9.

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Animal/Disease Models: Male balb/c (Bagg ALBino) mouse with asthma[1]
Doses: 150 µg/kg
Route of Administration: Nebulization
Experimental Results: diminished total cell number and relative eosinophil number in BALF .

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OVA-Induced Asthma Murine Model:
1. Sensitization: Female BALB/c mice (6–8 weeks old) were intraperitoneally injected with 10 μg OVA emulsified in aluminum hydroxide on day 0 and day 7.
2. Challenge: From day 14 to day 20, mice were exposed to 1% OVA aerosol (nebulization time: 30 minutes/day) to induce asthma.
3. Drug Administration: Beclomethasone dipropionate was dissolved in phosphate-buffered saline (PBS) containing 0.1% Tween 80. Mice in the treatment groups received ultrasonic nebulization of Beclomethasone dipropionate at 0.5, 1, or 2 mg/kg (nebulization time: 15 minutes/day) from day 14 to day 20 (once daily, concurrent with OVA challenge). The control group received nebulized PBS+0.1% Tween 80.
4. Sample Collection & Detection: On day 21, mice were euthanized. Bronchoalveolar lavage fluid (BALF) was collected to count inflammatory cells and measure cytokines (IL-4, IL-5) via ELISA. Lung tissues were fixed for histological staining (H&E and PAS) to assess inflammation and mucus secretion. Airway hyperresponsiveness (AHR) was measured 24 hours before euthanasia using a whole-body plethysmograph with methacholine (30 mg/mL) [1]

Absorption, Distribution and Excretion
Following oral inhalation of 320 mcg beclomethasone dipropionate (BDP), the peak plasma concentration (Cmax) was 88 pg/mL, reached 0.5 hours post-administration. The major and most active metabolite, beclomethasone 17-monopropionate (17-BMP), had a mean peak plasma concentration (Cmax) of 1419 pg/mL, reached 0.7 hours post-administration. In another pharmacokinetic study, the areas under the curve (AUC) for BDP and 17-BMP were 6660 pg·h/mL and 6185 pg·h/mL, respectively. The peak plasma concentration (Cmax) for BDP was 35356 pg/mL, and for 17-BMP it was 2633 pg/mL, with a median time to reach these concentrations (Tmax) of 0.2 hours. In the same study, the AUC of 17-BMP after oral and intranasal administration were 10158 and 3660 pg·h/mL, respectively. The Cmax of 17-BMP after oral and intranasal administration were 703 and 310 pg/mL, respectively, with a Tmax of 4 hours. The total bioavailability of 17-BMP after oral and intranasal administration was 41% and 44%, respectively. Regardless of the route of administration, beclomethasone dipropionate and its metabolites are primarily excreted in feces, with less than 10% excreted in urine. After intravenous administration, the steady-state volume of distribution (VHD) of beclomethasone dipropionate was 20 L, and that of its active metabolite, 17-monopropionate beclomethasone, was 424 L. After intravenous administration, the clearance rates of beclomethasone dipropionate and 17-BMP were 150 L/h and 120 L/h, respectively.

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Metabolic/Metabolic Substances During absorption, beclomethasone dipropionate undergoes rapid and extensive hydrolysis catalyzed by esterases. Beclomethasone is metabolized via CYP3A to beclomethasone 17-monopropionate (17-BMP), beclomethasone 21-monopropionate (21-BMP), and beclomethasone (BOH). 17-BMP is the major active metabolite with the strongest anti-inflammatory activity. After oral inhalation, approximately 95% of beclomethasone dipropionate undergoes first-pass metabolism in the lungs to generate 17-BMP.

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Biological Half-Life After intravenous administration, the half-life of beclomethasone dipropionate is 0.5 hours, while the half-life of the active metabolite 17-BMP is 2.7 hours. After oral and intranasal administration, the half-lives of 17-BMP are 8.8 hours and 5.7 hours, respectively.

Protein binding
According to in vitro studies, the protein binding rate of the main active metabolite beclomethasone-17-monopropionate (17-BMP) was 94-96% in the concentration range of 1000 to 5000 pg/mL.

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In vitro cytotoxicity: Beclomethasone dipropionate (10⁻⁹ to 10⁻⁶ M) did not affect the viability of human bronchial epithelial cells (cell viability >90% by MTT assay, compared with the control group)[2]
In vivo toxicity: In the beclomethasone dipropionate treatment group (0.5–2), no significant changes in mouse body weight or signs of hepatotoxicity (e.g., abnormal serum ALT, AST, BUN levels) were observed. Compared with the control group, mg/kg)[1]

[1]. Applicability of an ultrasonic nebulization system for the airways delivery of beclomethasone dipropionate in a murine model of asthma. Pharm Res. 2006 Aug;23(8):1765-75.

[2]. Beclomethasone dipropionate and formoterol reduce oxidative/nitrosative stress generated by cigarette smoke extracts and IL-17A in human bronchial epithelial cells. Eur J Pharmacol. 2013 Oct 15;718(1-3):418-27.

According to state or federal labeling requirements, beclomethasone dipropionate may cause developmental toxicity. Beclomethasone dipropionate is a steroidal ester composed of beclomethasone with propionyl groups at positions 17 and 21. It is used as an anti-inflammatory, anti-asthmatic, prodrug, and antiarrhythmic agent. It is a steroidal ester, enone, 20-oxosteroid, 11β-hydroxysteroid, propionate, corticosteroid, glucocorticoid, 3-oxo-Δ1,Δ4-steroid, and chlorosteroid. It is functionally related to beclomethasone. Beclomethasone dipropionate is a second-generation synthetic corticosteroid, a diester of beclomethasone, and structurally similar to dexamethasone. Beclomethasone dipropionate is a prodrug of its active metabolite, beclomethasone monopropionate (17-BMP), which acts on glucocorticoid receptors to exert its therapeutic effect. Beclomethasone dipropionate itself has a weak affinity for glucocorticoid receptors and is rapidly converted to 17-BMP after administration. Beclomethasone dipropionate is available in various formulations, including inhalation, nasal, and topical administration. It was first marketed as a metered-dose inhaler in 1972, followed by dry powder inhalers and aqueous nasal sprays. Due to its anti-inflammatory, antipruritic, and anti-allergic properties, beclomethasone dipropionate is used to treat various inflammatory diseases, such as asthma, allergic rhinitis, and skin diseases, to relieve symptoms. After inhalation, beclomethasone dipropionate is believed to remain locally active in the lungs without causing the significant side effects associated with systemic glucocorticoids. Compared to earlier glucocorticoids (such as dexamethasone and prednisolone), beclomethasone dipropionate has been reported to be less irritating to the nasal mucosa and have a longer duration of action when administered intranasally. Beclomethasone dipropionate is a dipropionate of a synthetic glucocorticoid with anti-inflammatory and immunomodulatory properties. Beclomethasone binds to cell surface receptors and enters the cell, then into the nucleus, where it binds to and activates specific nuclear receptors, thereby altering gene expression and inhibiting the production of pro-inflammatory cytokines. It is an anti-inflammatory synthetic glucocorticoid. It can be used topically as an anti-inflammatory drug and also as an aerosol for the treatment of asthma.
See also: Beclomethasone (containing the active ingredient); Beclomethasone 17-monopropionate (containing the active ingredient); Beclomethasone dipropionate monohydrate (note moved here).

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Indications
For maintenance treatment of asthma in patients aged 5 years and older, and as a preventative treatment, administered via oral inhalation. Beclomethasone dipropionate aerosol is not indicated for the relief of acute bronchospasm. Intranasal administration is indicated for the relief of symptoms of seasonal or perennial allergic and non-allergic (vasomotor) rhinitis and for the prevention of recurrence after surgical removal of nasal polyps. Indications for the relief of inflammatory and itchy symptoms of skin conditions responsive to corticosteroids in patients aged 13 years and older. Skin conditions responding to corticosteroids include psoriasis, contact dermatitis, atopic dermatitis (infantile eczema, allergic dermatitis), neurodermatitis (chronic simple lichen, lichen planus, eczema, eczematous dermatitis), chafing, pompholyx, seborrheic dermatitis, exfoliative dermatitis, photodermatitis, eczematous dermatitis, and anogenital pruritus and senile pruritus.

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Mechanism of Action
Beclomethasone dipropionate is a corticosteroid prodrug that can be rapidly activated by hydrolysis to the active monoester 17-monopropionate (17-BMP), which mediates anti-inflammatory effects. In vitro studies have shown that 17-BMP has approximately 13 times the binding affinity to human glucocorticoid receptors as dexamethasone and 25 times that of beclomethasone dipropionate. Upon ligand binding, the glucocorticoid receptor dimers and translocates to the nucleus, subsequently binding to the glucocorticoid response element (GRE) on glucocorticoid response genes, leading to transcriptional alterations. Several mechanisms by which glucocorticoids exert their anti-inflammatory effects have been proposed. Glucocorticoids may exert their effects by increasing the transcription of genes encoding anti-inflammatory proteins, including lipocortin-1 and interleukin-10. Furthermore, glucocorticoids have been shown to inhibit the expression of genes encoding various pro-inflammatory factors, such as cytokines, chemokines, and adhesion molecules, which are activated during chronic inflammation. This is thought to be due to a direct inhibitory interaction between activated glucocorticoid receptors and activated pro-inflammatory transcription factors, such as nuclear factor-κB and activator protein-1. Chronic inflammation is typically characterized by enhanced expression of these transcription factors, which bind to and activate coactivators, then acetylate core histones to initiate gene transcription, thereby further amplifying the inflammatory process. Corticosteroids inhibit the expression of a variety of inflammatory genes by promoting histone deacetylation, resulting in tighter DNA wrapping and reduced contact between transcription factors and their binding sites.

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Drug background: Beclomethasone dipropionate is an inhaled corticosteroid (ICS) widely used to treat asthma and chronic obstructive pulmonary disease (COPD)[1][2]
-Mechanism of action: Beclomethasone dipropionate exerts its anti-inflammatory effect by inhibiting the activation of nuclear factor-κB (NF-κB), thereby reducing the production of pro-inflammatory cytokines (IL-4, IL-5, IL-8) and oxidative stress mediators (ROS, NO)[2]
-Administration advantages: Ultrasonic nebulization is an effective way to deliver beclomethasone dipropionate to the airways because it can generate tiny aerosol droplets (median mass 100 μm. Aerodynamic diameter: 3.2 μm) that can reach the lower respiratory tract, enhancing the therapeutic effect in asthma models[1]

C28H37CLO7

521.04

520.222

5534-09-8

Betamethasone dipropionate;5593-20-4;Beclometasone dipropionate-d10;Beclometasone;4419-39-0;Beclometasone dipropionate-d6;Beclometasone dipropionate monohydrate;77011-63-3

21700

White to off-white solid powder

1.3±0.1 g/cm3

630.5±55.0 °C at 760 mmHg

210ºC

335.1±31.5 °C

0.0±4.2 mmHg at 25°C

1.564

4.59

1

7

8

36

1050

8

CCC(=O)OCC(=O)[C@]1([C@H](C[C@@H]2[C@@]1(C[C@@H]([C@]3([C@H]2CCC4=CC(=O)C=C[C@@]43C)Cl)O)C)C)OC(=O)CC

KUVIULQEHSCUHY-XYWKZLDCSA-N

InChI=1S/C28H37ClO7/c1-6-23(33)35-15-22(32)28(36-24(34)7-2)16(3)12-20-19-9-8-17-13-18(30)10-11-25(17,4)27(19,29)21(31)14-26(20,28)5/h10-11,13,16,19-21,31H,6-9,12,14-15H2,1-5H3/t16-,19-,20-,21-,25-,26-,27-,28-/m0/s1

(8S,9R,10S,11S,13S,14S,16S,17R)-9-chloro-11-hydroxy-10,13,16-trimethyl-3-oxo-17-[2-(propionyloxy)acetyl]-6,7,8,9,10,11,12,13,14,15,16,17-dodecahydro-3H-cyclopenta[a]phenanthren-17-yl propionate

2934.99.9001

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)

Solubility in Formulation 1: ≥ 2.5 mg/mL (4.80 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 2: ≥ 2.5 mg/mL (4.80 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

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 (Please use freshly prepared in vivo formulations for optimal results.)