Application of cysteamine hydrochloride in preparation of medicine for treating diabetic nephropathy
By using cysteine hydrochloride as a drug component and administering it by injection, the problems of glomerular enlargement, mesangial proliferation, and proteinuria in diabetic nephropathy have been resolved, providing an effective treatment option.
Patent Information
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2026-03-17
- Publication Date
- 2026-04-21
AI Technical Summary
Current technologies are insufficient to effectively treat diabetic nephropathy, especially to reduce proteinuria caused by glomerular enlargement, glomerular mesangial proliferation, and kidney damage.
Cysteine hydrochloride is used as the active ingredient and is administered via intraperitoneal, subcutaneous, intravenous, intramembranous, or intramuscular injection at a concentration of 30 mg/kg. It is used to prepare a drug for the treatment of diabetic nephropathy.
Cysteine hydrochloride can reduce glomerular enlargement and glomerular mesangial proliferation, improve proteinuria caused by kidney damage, and provide a new treatment option for diabetic nephropathy.
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Figure CN121891345A_ABST
Abstract
Description
Technical Field
[0001] This invention relates to the field of pharmaceutical technology, specifically to the application of cysteine hydrochloride in the preparation of drugs for treating diabetic nephropathy. Background Technology
[0002] Diabetic nephropathy is a chronic disease caused by diabetes mellitus characterized by damage to the kidney structure and decline in function. The clinical manifestations are persistent albuminuria, decreased glomerular filtration rate, or both. When the random urine albumin / creatinine ratio is ≥30 mg / g or the urine albumin excretion rate is ≥30 mg / 24 h, and the UACR is repeated within 3 to 6 months, and 2 out of 3 times it reaches or exceeds the critical value; other interfering factors such as infection are excluded, or the glomerular filtration rate is lower than 60 ml / min / 1.73 m² for more than 3 months, and the kidney biopsy is consistent with the pathological changes of DN, a diagnosis should be considered. Diabetic nephropathy is the most common cause of end-stage renal disease worldwide. Its prevalence has increased sharply with the diabetes epidemic, causing a heavy disease burden and medical expenditure, and has become one of the important chronic diseases that seriously affect public health[1].
[0003] In diabetic nephropathy, hyperglycemia directly leads to excessive production of reactive oxygen species (ROS) by kidney cells, triggering oxidative stress, damaging kidney podocytes, damaging the glomerular filtration barrier, resulting in proteinuria and continuous loss of kidney function [2].
[0004] Cysteine is a key precursor for the synthesis of the antioxidant glutathione (GSH). In diabetic nephropathy, the increase in renal GSH levels can directly neutralize excess reactive oxygen species, thereby reducing oxidative stress damage and inhibiting inflammation and cell death [3]. Cysteine hydrochloride, as a derivative of cysteine, can be used for the drug treatment of cystinosis [4]. The application of cysteine hydrochloride to improve the occurrence and progression of diabetic nephropathy and to provide a more convenient, efficient and economical treatment method has important clinical value. Therefore, this invention is proposed.
[0005] The above references are: 1. Kidney Disease: Improving Global Outcomes (KDIGO) Diabetes WorkGroup. KDIGO 2020 Clinical Practice Guideline for Diabetes Management inChronic Kidney Disease. Kidney Int. 2020 Oct;98(4S):S1-S115. doi: 10.1016 / j.kint.2020.06.019. PMID: 32998798. 2. Samsu N. Diabetic Nephropathy: Challenges in Pathogenesis, Diagnosis, and Treatment. Biomed Res Int. 2021 Jul 8;2021:1497449. doi:10.1155 / 2021 / 1497449. PMID: 34307650; PMCID: PMC8285185. 3. Zhong S, Wang N, Zhang C. Podocyte Death in Diabetic KidneyDisease: Potential Molecular Mechanisms and Therapeutic Targets. Int J MolSci. 2024 Aug 20;25(16):9035. doi: 10.3390 / ijms25169035. PMID: 39201721; PMCID: PMC11354906. 4. Carneiro A, Jones DH. Advances in Pharmacological Treatments for Cystinosis: Cysteamine and Its Alternatives. ACS Pharmacol Transl Sci. 2026Jan 15;9(2):272-281. doi: 10.1021 / acsptsci.5c00633. PMID: 41710743; PMCID: PMC12910489. Summary of the Invention
[0006] The purpose of this invention is to provide the application of cysteine hydrochloride in the preparation of drugs for diabetic nephropathy, expand the pharmaceutical applications of cysteine hydrochloride, and provide a new solution for the treatment of diabetic nephropathy.
[0007] To achieve the above and other related objectives, the first aspect of the present invention provides the use of cysteine hydrochloride in the preparation of a medicament for treating or delaying diabetic nephropathy.
[0008] A second aspect of the present invention provides the use of cysteine hydrochloride in the preparation of a medicament for reducing glomerular enlargement and / or glomerular mesangial proliferation.
[0009] A third aspect of the present invention provides the use of cysteine hydrochloride in the preparation of a medicament for alleviating proteinuria caused by kidney damage.
[0010] A fourth aspect of the present invention provides a medicament for treating or delaying diabetic nephropathy, wherein the medicament is composed of cysteine hydrochloride as an active ingredient.
[0011] Furthermore, the concentration of cysteine hydrochloride in the drug is 30 mg / kg. Furthermore, the administration method of the drug is selected from at least one of intraperitoneal injection, subcutaneous injection, intravenous injection, intramural injection, intramuscular injection, and intrasternal injection.
[0012] As described above, the application of cysteine hydrochloride of the present invention in the preparation of a medicament for treating diabetic nephropathy has the following effective effects: The cysteine hydrochloride provided by this invention can be used to treat and delay diabetic nephropathy, expanding the application field of cysteine hydrochloride and providing a new solution for the treatment of diabetic nephropathy.
[0013] This invention has found that cysteamine hydrochloride can reduce glomerular enlargement and glomerular mesangial proliferation, and improve proteinuria caused by kidney damage. Therefore, cysteamine hydrochloride can be used to treat and delay diabetic nephropathy. Attached Figure Description
[0014] Figure 1 Randomization and drug intervention timeline for db / db mice Figure 2 The intraperitoneal glucose tolerance test, insulin sensitivity test, and fasting blood glucose levels were compared between the db / db control group and the cysteine hydrochloride supplementation group. Figure 3 HE and PAS staining were used to detect the improvement in glomerular area and mesangial matrix in the db / db control group and the cysteine supplementation group. Figure 4 The UACR ratio between the db / db control group and the cysteine supplementation group. Detailed Implementation
[0015] The present invention will be described in detail below with reference to specific embodiments and examples, thereby making its advantages and various effects more clearly apparent. Those skilled in the art should understand that these specific embodiments and examples are illustrative of the invention and not intended to limit it. Throughout this specification, unless otherwise specified, the terminology used herein should be understood as it is commonly used in the art. Therefore, unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by those skilled in the art to which this invention pertains. In case of any conflict, this specification takes precedence. Unless otherwise specified, all raw materials, reagents, instruments, and equipment used in this invention are commercially available or obtainable by existing methods. The application of the cysteine hydrochloride of this application in the preparation of a medicament for the prevention or treatment of diabetic nephropathy will be described below with examples and experimental data. Example 1: Cysteine hydrochloride was used to treat glomerular enlargement and mesangial proliferation in mice.
[0016] Preparation method of cysteamine hydrochloride reagent: Weigh 100 mg of cysteine hydrochloride (Merck, 30078) and dissolve it in 100 μl of physiological saline. Then, use 1900 μl of physiological saline to prepare a 5 mg / ml solution and store it at -20°C protected from light.
[0017] Thaw the cysteamine hydrochloride solution to room temperature on the day of use.
[0018] Experimental subjects: Eight male db / db mice weighing 35g were selected.
[0019] Experimental methods: db / db mice were randomly divided into two groups of four. The experimental group mice were injected intraperitoneally with cysteine hydrochloride, 30 mg / kg, once a day for seven days, with a two-day break after five days of injection, for a total of 12 weeks.
[0020] Figure 1 The timeline shows mouse grouping and cysteine hydrochloride administration intervention.
[0021] Control group mice were injected with physiological saline. At 20 weeks, mice were sacrificed after urine was collected. Kidney tissue was harvested, embedded, sectioned, and stained with H&E and PAS to observe the pathological structure of the kidney tissue.
[0022] Experimental results: Figure 2The images show H&E staining and volume statistics of glomeruli in mice with cysteine hydrochloride-based nephropathy. A shows the pathological tissue structure of mouse glomeruli as detected by H&E staining; B shows the volume statistics of mouse glomeruli; C shows the area of mesangial proliferation in mouse glomeruli as detected by PAS staining; and D shows the statistics of mesangial proliferation in mouse glomeruli.
[0023] Depend on Figure 2 It can be seen that treatment with cysteine hydrochloride can reduce the increase in glomerular volume and mesangial proliferation in diabetic nephropathy mice.
[0024] Example 3: Cysteine hydrochloride was used to treat proteinuria caused by kidney damage in diabetic nephropathy mice.
[0025] Experimental subject: Urine from 20-week-old mice in Example 1.
[0026] Experimental methods: Mouse urine was collected, and mouse urine microalbumin (Elabscience) and creatinine (Nanjing Jiancheng) were detected using a kit. The UACR was calculated as microalbumin content / creatinine content.
[0027] Experimental results: Figure 3 The figure shows the UACR value of hemiluminamine hydrochloride in improving proteinuria caused by kidney damage in diabetic nephropathy mice. Figure 3 It is known that semiamine hydrochloride can reduce the amount of protein in urine caused by kidney damage in diabetic nephropathy mice and improve the proteinuria in diabetic nephropathy mice.
[0028] Example 4: Cysteine hydrochloride application does not affect pancreatic islet function in db / db mice.
[0029] Experimental subjects: Mice in the 20-week control group and the cysteine hydrochloride supplementation group.
[0030] Experimental methods: Intraperitoneal glucose tolerance test: Mice were fasted the night before the experiment for 12-16 hours, during which time they were allowed free access to water. 2g of glucose was weighed, dissolved, and diluted to 10ml of sterile physiological saline, and injected intraperitoneally into the mice at a dose of 2g / kg body weight. Blood glucose levels were measured at 0 min, 15 min, 30 min, 60 min, and 120 min.
[0031] Insulin sensitivity test: Mice were fasted for 4-6 hours around 10:00 AM on the day of the experiment, but given free access to water. The undiluted insulin solution (400 IU / 10 ml) was diluted 400 times with sterile saline to 0.1 IU / ml, and injected intraperitoneally at a dose of 0.5 IU / kg body weight. Blood glucose levels were measured at 0, 15, 30, 60, and 120 minutes. If any mouse showed signs of hypoglycemia due to insulin hypersensitivity, glucose was injected intraperitoneally immediately to monitor the mouse's condition, and the experiment was terminated.
[0032] Experimental results: Figure 4 The results show glucose tolerance and insulin sensitivity in mice after intraperitoneal injection of semiamine hydrochloride and in the control group. A represents the glucose tolerance results and area under the curve (AUC) for both groups; B represents the insulin sensitivity results and AUC for both groups; and C represents the percentage insulin sensitivity results and AUC for both groups. Figure 4 It can be seen that semiamine hydrochloride does not affect intraperitoneal glucose tolerance and insulin sensitivity in mice, suggesting that semiamine hydrochloride does not affect the insulin sensitivity and glucose tolerance that db / db mice originally possess.
[0033] In summary, this invention, through experiments using a db / db mouse model, found that cysteamine hydrochloride does not alter insulin sensitivity or glucose tolerance in db / db mice, but it can improve glomerular enlargement and mesangial proliferation in diabetic nephropathy mice, and simultaneously improve proteinuria caused by kidney damage in diabetic nephropathy. Therefore, cysteamine hydrochloride can be used to treat and delay the progression of diabetic nephropathy. This invention provides a new treatment option for diabetic nephropathy and is beneficial for its advancement.
[0034] The above embodiments are merely illustrative of the principles and effects of the present invention and are not intended to limit the invention. Any person skilled in the art can modify or alter the above embodiments without departing from the spirit and scope of the present invention. Therefore, all equivalent modifications or alterations made by those skilled in the art without departing from the spirit and technical concept disclosed in the present invention should still be covered by the claims of the present invention.
Claims
1. The use of cysteine hydrochloride in the preparation of drugs for the treatment or delay of diabetic nephropathy.
2. Use of cysteine hydrochloride in the preparation of drugs for reducing glomerular enlargement and / or glomerular mesangial proliferation.
3. The use of cysteine hydrochloride in the preparation of drugs for reducing proteinuria caused by kidney damage.
4. A drug for treating or delaying diabetic nephropathy, characterized in that: The drug uses cysteine hydrochloride as its active ingredient.
5. The application as described in claim 4, characterized in that: The concentration of cysteine hydrochloride in the drug is 30 mg / kg.
6. The application as described in claim 5, characterized in that, The administration method of the drug is selected from at least one of intraperitoneal injection, subcutaneous injection, intravenous injection, intraperitoneal injection, intramuscular injection, and intrasternal injection.