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C-peptide spray is a novel mucosal drug delivery formulation developed with natural c-peptide composed of 31 amino acids as the core raw material. It is refined via a liquid-phase continuous-flow synthesis process and compounded with excipients including mucosal absorption enhancers and stabilizers. Leveraging the atomization advantage of fine spray droplets, the formulation acts on the nasal and oral mucosa, bypassing the gastrointestinal first-pass effect. It requires no venous blood collection or puncture, featuring non-invasive and convenient administration.
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Application in Etiological Differentiation of Hypoglycemia
Hypoglycemia is a common acute endocrine emergency in clinical practice with complex etiologies, mainly classified into insulin-mediated and non-insulin-mediated types. Therapeutic regimens vary significantly for different causes, and accurate etiological differentiation is the key to clinical treatment.
As a specific biomarker for endogenous insulin secretion by pancreatic β-cells, plasma it concentration is not interfered by exogenous insulin. Compared with insulin detection, it can more accurately reflect the functional status of pancreatic β-cells.
C-peptide spray enables rapid mucosal absorption to quickly obtain plasma the peptide concentration, providing timely and reliable detection evidence for the etiological differentiation of hypoglycemia, especially suitable for rapid diagnosis of emergency patients.
Excessive exogenous insulin is one of the most common causes of hypoglycemia, mostly occurring in diabetic patients during insulin therapy or due to artificial overdose insulin injection. During an episode, such patients present with blood glucose ≤ 70 mg/dL and significantly elevated plasma insulin concentration.
In clinical practice, it is promptly administered to patients with hypoglycemic symptoms such as sweating, trembling and confusion for detection of plasma the peptide and insulin levels. The characteristic manifestation of elevated insulin and decreased it, combined with the patient's insulin medication history, enables a definitive diagnosis of exogenous insulin overdose without further complicated examinations, supporting timely insulin dose adjustment and hypoglycemia correction.
Insulinoma is a rare cause of hypoglycemia, a benign tumor of pancreatic β-cells. Tumor cells continuously and autonomously secrete large amounts of insulin, leading to recurrent fasting or postprandial hypoglycemia.
During episodes, patients show significantly lowered blood glucose along with marked elevation of both plasma insulin and it concentrations. A plasma c-peptide level > 200 pmol/L is a characteristic indicator of insulinoma. Combined with pancreatic space-occupying lesions detected by abdominal CT, MRI and other imaging examinations, a definitive diagnosis can be made.
It allows rapid detection of plasma it concentration. Compared with traditional venous blood sampling, it is puncture-free and easy to operate, delivering test results quickly during hypoglycemic episodes and avoiding diagnostic delays caused by delayed blood collection.

It can also be used for postoperative recurrence monitoring of insulinoma; persistently elevated postoperative it concentration indicates tumor residue or recurrence.
Non-insulin-mediated hypoglycemia results from abnormal functions of non-pancreatic β-cells. Common causes include adrenal insufficiency, liver failure, severe malnutrition, sepsis, etc. Hypoglycemic episodes in such patients are unrelated to insulin secretion, resulting in normal or low plasma insulin and normal or decreased the peptide levels.
Taking adrenal insufficiency as an example, insufficient secretion of adrenocortical hormones weakens the body's anti-insulin effect and lowers blood glucose, while pancreatic β-cell insulin secretion function remains normal with plasma it at a normal level. For patients with liver failure, reduced hepatic glycogen synthesis and reserve capacity fail to replenish blood glucose in a timely manner, and the liver's insulin inactivation capacity declines. Nevertheless, pancreatic β-cells maintain balance by regulating insulin secretion, leading to mostly normal or slightly decreased plasma it concentration. It can rapidly distinguish such causes from insulin-mediated hypoglycemia, clarifying the direction for clinical treatment of primary diseases.
Data source: Hypoglycemia – Endocrine and Metabolic Disorders[EB/OL]. December 1, 2025; Medscape. C-Peptide[EB/OL]. November 11, 2025; PMC. The evolution of C-peptide's role in diabetes care[J].
Application in Postoperative Monitoring of Islet/Pancreatic Transplantation
Islet/pancreatic transplantation is an effective treatment for end-stage diabetes. Its core goal is to reconstruct patients' pancreatic β-cell function, realize autonomous insulin secretion and eliminate dependence on exogenous insulin. Postoperative monitoring of the survival status and functional recovery of pancreatic β-cells is critical for judging transplant success and early detection of rejection. As a specific biomarker of pancreatic β-cell function, changes in c-peptide concentration reflect the functional status of transplanted islets earlier than blood glucose abnormalities. With the advantages of rapid absorption and convenient operation, c-peptide spray has become an important tool for postoperative monitoring of islet/pancreatic transplantation.
The core marker of successful islet/pancreatic transplantation is the survival and functional reconstruction of transplanted pancreatic β-cells. In clinical monitoring, a postoperative c-peptide concentration > 0.5 nmol/L with sustained stability is an important indicator of transplant success. Regular administration of it for plasma the peptide detection shows that a gradual rise and stable maintenance of it above 0.5 nmol/L, along with normal blood glucose levels without exogenous insulin therapy, indicates the successful survival of transplanted pancreatic β-cells with normal insulin secretory function. Compared with traditional venous blood sampling for it detection, the spray relieves patients from puncture pain and improves compliance with postoperative long-term follow-up monitoring.


Rejection is a major complication after islet/pancreatic transplantation. Failure to detect and intervene in a timely manner will lead to loss of transplanted islet function and ultimately transplant failure. During rejection, transplanted pancreatic β-cells are attacked by the immune system with impaired function and reduced insulin secretion, accompanied by progressive decline in plasma c-peptide concentration - a change occurring 3–7 days earlier than blood glucose abnormalities. Therefore, the spray enables early warning of rejection.Clinically, regular postoperative it detection via the spray is recommended. Persistently declining it concentration, even with normal blood glucose, requires high vigilance for potential rejection.
Timely adjustment of immunosuppressive therapy and anti-rejection treatment can effectively reverse islet function damage and improve transplant success rates.
In clinical application, combined with imaging examination, blood glucose monitoring and immune index detection, the spray forms a comprehensive postoperative monitoring system, providing multi-dimensional evidence for clinical evaluation of transplant efficacy and complication intervention. Compared with traditional monitoring methods, it features simple operation, non-invasiveness and rapid detection, significantly improving postoperative monitoring efficiency and alleviating patient suffering, which is of great significance for optimizing the prognosis of patients undergoing islet/pancreatic transplantation.

Data source: PubMed. Home urine C-peptide creatinine ratio can be used to monitor islet transplant function[J]; PMC. The evolution of C-peptide's role in diabetes care[J].

The synthesis process of the product is mainly divided into two stages: raw material synthesis and formulation preparation.
Raw material synthesis adopts an automated liquid-phase continuous-flow synthesis system, which consists of an amidation unit, extraction unit, concentration unit and control unit. It enables continuous production from amino acid raw materials to crude peptide, reducing manual intervention and human error. The amidation reaction is carried out in a microfluidic reactor.
Appropriate condensing agents are selected to promote peptide bond formation between amino acids and avoid racemization. The extraction unit separates the target peptide from reaction waste liquid via a mixer-settler, while the concentration unit adopts a thin-film evaporator for rapid concentration of crude peptide to further increase product concentration.
The key to the formulation preparation stage lies in optimizing the prescription composition to improve the mucosal absorption efficiency of c-peptide and formulation stability. Non-ionic surfactants or bile salts are selected as absorption enhancers to reduce mucosal barrier resistance and facilitate the trans-mucosal transport of c-peptide.
Mannitol, trehalose and other substances are used as stabilizers to inhibit the aggregation and degradation of c-peptide peptide chains and extend the shelf life of the formulation. Osmotic pressure regulators ensure the spray formulation matches the osmotic pressure of human mucosa and reduce mucosal irritation.
In addition, it is necessary to optimize spray particle size and injection pressure to form uniform fine droplets, expand the contact area with the mucosa and accelerate absorption.
Optimization of process parameters enables the spray to achieve effective plasma concentration within 15–30 minutes after administration, meeting clinical demands for rapid monitoring and auxiliary diagnosis.
Data source: December 16, 2022; PubMed. Syntheses of C-peptides and human proinsulin[J]; Pepcodex.com. Peptide Nasal Spray for Migraine Prevention Enters Phase 2[J]. October 17, 2025.
FAQ
What is the role of the C-peptide?
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Firstly, C-peptide enhances microvascular blood flow and improves microvascular endothelial function. It increases microvascular blood flow and mitigates vascular permeability by activating eNOS (62).
What conditions cause high C peptides?
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The normal physiological C-peptide plasma concentration in a fasted state is 0.9 to 1.8 ng/ml. [1] A high level could indicate insulin resistance, insulinoma, or kidney disease.
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