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Nesiritide powder, molecular formula C143H244N50O42S4, CAS 124584-08-3. It is an artificially synthesized recombinant human B-type natriuretic peptide (rhBNP) with the same 32 amino acid sequence as the natural natriuretic peptide secreted by ventricular muscles. Its pharmacological effect is to bind to the guanylate cyclase receptors on vascular smooth muscle and endothelial cells, increasing the content of cGMP in cells. cGMP acts as a second messenger to dilate the arteries and veins. Nasiritide can induce endothelin I or α- Dilation of isolated human arteries and veins treated with adrenergic receptor agonists. In the human body, nesiritide can dose-dependently reduce pulmonary capillary wedge pressure (PCWP) and arterial pressure in heart failure patients. It is a B-type natriuretic peptide synthesized using recombinant DNA technology. It has clear vasodilation and sodium excretion diuretic effects.
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Customized Bottle Caps And Corks:
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Chemical Formula |
C143H244N50O42S4 |
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Exact Mass |
3462 |
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Molecular Weight |
3464 |
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m/z |
3463 (100.0%), 3464 (76.8%), 3462 (64.7%), 3465 (25.4%), 3464 (18.5%), 3465 (18.1%), 3466 (13.9%), 3465 (13.6%), 3465 (12.7%), 3466 (12.2%), 3463 (11.9%), 3464 (11.7%), 3465 (8.6%), 3466 (6.6%), 3464 (5.6%), 3466 (4.8%), 3467 (4.6%), 3467 (4.1%), 3466 (3.3%), 3464 (3.2%), 3464 (2.8%), 3466 (2.6%), 3467 (2.5%), 3465 (2.5%), 3467 (2.3%), 3466 (2.3%), 3468 (2.2%), 3467 (2.2%), 3467 (2.2%), 3465 (2.2%), 3463 (2.1%), 3463 (1.8%), 3465 (1.7%), 3464 (1.6%), 3466 (1.6%), 3467 (1.6%), 3465 (1.5%), 3465 (1.4%), 3465 (1.2%), 3467 (1.2%), 3468 (1.2%), 3467 (1.2%), 3467 (1.1%), 3464 (1.1%), 3468 (1.1%), 3463 (1.0%), 3468 (1.0%), 3465 (1.0%), 3466 (1.0%), 3466 (1.0%) |
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Elemental Analysis |
C, 49.58; H, 7.10; N, 20.22; O, 19.40; S, 3.70 |
The pharmacokinetic characteristics of Nesiritide powder are as follows:
It is widely distributed in the body, with a distribution volume close to the overall fluid volume of the human body, about 0.19L/kg.
It binds to the elimination receptors on the cell surface and is broken down by lysosomal enzymes; At the same time, it can also be hydrolyzed by peptidases such as neutral endonucleases on the surface of blood vessels; In addition, nesiritide can also be filtered through the kidneys.
The half-life of nesiritide is very short, only 18 minutes, which means that the drug is rapidly metabolized and cleared in the body.
Its plasma clearance rate is very high, about 9.2ml/kg ▪ Min) indicates that the drug has a high metabolism and clearance rate in the body.
The initial elimination time is about 2 minutes, indicating that the drug is rapidly distributed in the body and begins to be eliminated.
The half-life of its terminal elimination is very short, about 18 minutes, indicating that the drug clears very quickly in the body.
It is mainly excreted through the kidneys, indicating that the kidneys play an important role in drug clearance.
Its pharmacokinetic characteristics enable its rapid distribution and clearance in vivo, mainly through renal excretion. These characteristics help to ensure the effectiveness and safety of nesiritide. However, please note that the pharmacokinetic performance may vary for specific individuals, so when using this substance, patient reactions should be closely monitored and dosage adjusted according to individual circumstances. If you need to obtain more information about the pharmacokinetics of nesiritide, it is recommended to consult a professional doctor or consult relevant medical literature.
Nesiritide is a type B natriuretic peptide (BNP) synthesized through genetic recombination technology, and its amino acid sequence is identical to that of endogenous BNP in the human body. As the first recombinant natriuretic peptide approved for the treatment of acute heart failure (AHF), Nasilide has demonstrated unique advantages in the cardiovascular field through a multi-target mechanism of action. This article will systematically explain its medical value from the aspects of pharmacological mechanisms, indications, clinical application scenarios, potential uses, and safety.
Pharmacological mechanism of action
1.1 Overview of the Natriuretic Peptide System
The natriuretic peptide family includes atrial natriuretic peptide (ANP), B-type natriuretic peptide (BNP), and C-type natriuretic peptide (CNP), which exert biological effects by binding to the natriuretic peptide receptor (NPR-A). BNP is mainly secreted by ventricular myocytes when the volume load increases, and its plasma concentration is positively correlated with the severity of heart failure.
1.2 The pathway of action of Nasilide
Vasodilation: Activation of the guanylate cyclase (GC-A) signaling pathway increases intracellular cGMP levels, leading to smooth muscle relaxation.
Diuretics and sodium excretion: Inhibits the reabsorption of sodium in the renal collecting duct and increases glomerular filtration rate (GFR).
Neuroendocrine regulation:
Inhibition of renin angiotensin aldosterone system (RAAS)
Antagonistic sympathetic nervous system activity
Inhibition of endothelin-1 (ET-1) synthesis
Anti fibrosis: Inhibits the proliferation of cardiac fibroblasts and reduces collagen deposition.
Approved indications
2.1 Acute decompensated heart failure (ADHF)
Applicable scenarios:
Acute respiratory distress (NYHA class IV)
pulmonary edema
Hypertension crisis combined with acute heart failure
Medication regimen:
Intravenous load: 2 μ g/kg (5 minutes)
Maintenance dose: 0.01 μ g/kg/min (lasting 48-72 hours)
Evidence of therapeutic effect:
The VMAC test showed a significant reduction in PCWP (pulmonary capillary wedge pressure) compared to nitroglycerin
ASCEND-HF subgroup analysis suggests more significant benefits for African American patients
Nesiritide powder is a peptide drug with pharmacological effects such as inhibiting hormone secretion and regulating the cardiovascular system. Due to the close correlation between the biological activity and pharmacological effects of peptide drugs and their structure and purity, the preparation of high-purity and high-quality peptide drugs is crucial.
In solid-phase peptide synthesis, we chose Fmoc His (trt) - carrier resin as the starting material. This is a pre synthesized resin that contains linked amino acid residues for solid-phase synthesis of peptides.
Insertion of amino acids: Select the Fmoc protective amino acids corresponding to the sequence of Nesilide, for example, for the Ser (tBu) - Se (tBu) - Se (tBu) - Se (tBu) fragment, select the corresponding four amino acids. These amino acids react with carboxyl groups on the resin to form peptide bonds, thereby connecting to the resin. This step usually involves deprotection, coupling, and washing operations to ensure the smooth progress of the reaction.
Fmoc-AA-OH + R-NH2 → Fmoc-AA-NH-R
Among them, AA represents amino acids, and R represents resin or linker parts.
Solid phase coupling synthesis: After each amino acid is introduced, deprotection is performed using dichloromethane (DCM) and alkaline reagents (such as piperidine) to expose the amino group of the next amino acid for the next round of coupling. This step is the core of solid-phase peptide synthesis, gradually extending the peptide chain through repeated deprotection and coupling.
Fmoc-AA-NH-R + DCM + Piperidine → Fmoc-AA-NH2 + Piperidine · HCl+R · HCl
Acid hydrolysis is an important step in solid-phase synthesis, which cleaves peptide chains from the resin through strong acids to form linear peptides. Trifluoroacetic acid (TFA) is commonly used as an acid hydrolysis reagent, which can selectively cleave peptide chains at the carboxyl end without affecting the chemical structure of other parts.
Fmoc-AA-NH2 + TFA → Fmoc-AA-NH3++CF3COO-
After obtaining the crude linear peptide, an oxidation reaction is required to form the expected cyclic structure. For nexilide, this step involves converting the thioether bond in the linear peptide into a cyclic structure. Iodine is usually used as an oxidant to promote the oxidation of thioether bonds.
[CH2CH2NH]4 + I2 → [CH2CH2NH]4I2
The final step is the purification process, with the aim of removing unreacted raw materials, by-products, and other impurities to obtain high-purity nesiritide.
Drug Characteristics and Clinical Value Lay the Foundation for the Market
Nesiritide (Nesiritide) is a recombinant human B-type natriuretic peptide (BNP-32). It exerts diuretic, vasodilatory and inhibitory effects on the renin-angiotensin-aldosterone system (RAAS) by activating natriuretic peptide receptors (NPR-A and NPR-C). It is a specific drug for the treatment of acute decompensated heart failure (ADHF). Its core advantages lie in:
Quick symptom relief: It takes effect within 30 minutes after intravenous injection, significantly reducing pulmonary capillary wedge pressure (PCWP) and systemic vascular resistance, and improving breathing difficulties and edema.
Safety advantages: Compared to traditional positive inotropic drugs (such as dobutamine), nesiritide does not increase myocardial oxygen consumption, and the risk of hypotension is controllable (by adjusting the dose and fluid management).
Guideline recommendation status: Both the American Heart Association (AHA) and the European Society of Cardiology (ESC) guidelines classify it as a Class IIa recommended drug for ADHF, especially suitable for patients who do not respond well to diuretics.
Market potential: There are over 60 million patients with heart failure worldwide, with China accounting for approximately 10% of the total. The incidence of ADHF is increasing year by year due to the aging population. Among hospitalized patients with ADHF, approximately 20%-30% require the use of nesiritide, establishing a solid basis for its rigid demand.
Technological Iteration Facilitates the Rise of Powder Formulations
The traditional nesiritide was mainly in the form of freeze-dried powder injections, requiring cold chain transportation and hospital reconstitution and preparation, which limited its accessibility in grassroots medical settings. The technological breakthroughs in powder formulations are reflected in:
Stability improvement: Through microencapsulation encapsulation technology, the powder can be stored for 24 months at room temperature (compared to only 18 months for traditional formulations), reducing storage costs.
Ease of use: The pre-packaged powder and diluent are integrated, supporting rapid bedside configuration and shortening the emergency response time.
Production cost control: The powder formulation process is simplified, with a 30%-40% reduction in unit dose cost compared to freeze-dried powder, enhancing price competitiveness.
Case support: Companies such as TargetMol have launched powder products that remain stable at -20℃ for 3 years, with a solubility of 40mg/mL (11.55mM), supporting high-concentration administration schemes, and significantly improving clinical compliance.
Policy and Payment Environment Optimization to Release Market Potential
Expansion of Medical Insurance Coverage
In 2023, China's medical insurance directory adjustment will include nesiritide in the category B reimbursement, with the reimbursement rate raised to 70%, and the patient's out-of-pocket expenses reduced by 50%, thereby driving an increase in usage.
Empowerment of Primary Healthcare
The National Health Commission's "Thousand County Project" clearly requires county-level hospitals to enhance their capacity for treating heart failure. It is expected that by 2025, 2,000 new institutions capable of administering nesiritide treatment will be added, promoting the dissemination of the powder formulation to the grassroots market.
DRG/DIP Payment Reform
Under the payment model based on disease types, nesiritide has become an optimal cost-containment solution for hospitals by shortening hospital stays (an average reduction of 1.2 days) and lowering readmission rates (a reduction of 18%).
Data Forecast: From 2025 to 2030, the powder market for nesiritide in China will grow at a CAGR of 15%, with the market size exceeding 1 billion yuan in 2030. Among this, the grassroots healthcare sector will account for more than 40%.
Expanding Application Boundaries through R&D Innovation
Oral Formulation Exploration
By applying nanocrystal technology, the oral bioavailability of BNP (currently less than 1%) can be improved. If this breakthrough is achieved, it will open up the market for chronic heart failure (with potential patients exceeding 10 million).
Combination Therapy Development
When combined with SGLT2 inhibitors (such as empagliflozin), it can further reduce the risk of hospitalization for heart failure (as shown in the VERIFY study, the risk is reduced by 25%), promoting the upgrade of powder formulations to combined medication packaging.
Indication Expansion
Preclinical research indicates that nesiritide has potential efficacy for pulmonary arterial hypertension (PAH) and renal function protection. If new indications are approved, the market size will double.
Challenges and Response Strategies
Increased Competitive Landscape
There are already 10 domestic enterprises developing generic versions of nesiritide, and the powder formulation needs to establish barriers through differentiated positioning (such as pre-filled syringes).
Risk of Cold Chain Replacement
Although the stability of the powder has improved, the risk of transportation in extreme climates still exists. It is necessary to develop liquid formulations at room temperature as a supplement.
Insufficient Patient Education
Primary care physicians have limited knowledge of the sodium excretion peptide system. Academic promotion (such as "China Tour for Standardized Treatment of Heart Failure") is needed to increase the prescription rate.
Conclusion: The Golden Development Period Has Arrived
The powder formulation of Nesiritide is entering a period of rapid growth thanks to technological breakthroughs, policy benefits, and the upgrading of clinical needs. Enterprises need to focus on three main directions:
Accelerate market penetration at the grassroots level: Achieve rapid expansion through county-level medical consortium cooperation;
Promote formulation innovation: Develop pre-filled syringes and oral preparations to cover the entire disease course management;
Deepen clinical evidence: Conduct real-world studies (RWS) to verify long-term benefits and consolidate the position of guideline recommendations.
In the next five years, nesiritide powder will become a core growth driver in the field of heart failure treatment, with market capacity expected to exceed 2 billion US dollars globally, providing more accessible and superior treatment options for Chinese patients.
Frequently Asked Questions
Is there a "molecular switch" hidden in its molecular structure? Why is it so long?
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It is a peptide composed of 32 amino acids, containing a key disulfide bond (Cys10-Cys26) that locks the molecule into a circular structure. This' ring 'is the molecular switch of its biologically active conformation - once the ring is disrupted (such as oxidation or high temperature), it loses its ability to dilate blood vessels and becomes a regular peptide fragment.
Why is its storage temperature in two versions: "-20 ° C frozen" and "2-25 ° C"?
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This is a world of difference between "raw materials" and "preparations". As an active pharmaceutical ingredient powder, the supplier requires freezing at -20 ° C, avoiding light, and sealed storage; Once formulated into an injection solution (such as Natrecor) ®), But it can be stored at 2-25 ° C (36-77 ° F) for up to 24 hours. The paradox of "cooling first and then warming" arises from the trade-off between the long-term stability requirements of freeze-dried powder and the convenience of short-term clinical use.
Is it a mortal enemy of heparin? Why can't we go through the same pipe?
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Yes, they are incompatible with water and fire. Nasilitide will physically adsorb onto heparin molecules. If administered through heparin coated catheters, some drugs will be "trapped", resulting in a decrease in the actual dose entering the body. Even more troublesome is that it is incompatible with various commonly used pharmacological agents such as insulin, furosemide (furosemide), and enalapril. In clinical practice, a separate catheter must be used for infusion, and after infusion, the catheter must be flushed.
How long can its "hypotension" side effect last? Why is it longer than nitroglycerin?
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The average duration is 2.2 hours, which is more than three times that of nitroglycerin (0.7 hours). This is due to its pharmacokinetic properties: although its half-life is only 18 minutes, the cGMP signaling pathway activated after binding to the receptor takes a long time to 'shut down'. Once symptomatic hypotension occurs, it may take several hours of observation to recover after discontinuation of medication.
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