CN103622992A - Application of hydrogen sulfide and donor thereof sodium hydrosulfide to preparation of medicament for treating diabetes - Google Patents
Application of hydrogen sulfide and donor thereof sodium hydrosulfide to preparation of medicament for treating diabetes Download PDFInfo
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- CN103622992A CN103622992A CN201210307009.8A CN201210307009A CN103622992A CN 103622992 A CN103622992 A CN 103622992A CN 201210307009 A CN201210307009 A CN 201210307009A CN 103622992 A CN103622992 A CN 103622992A
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Abstract
The invention belongs to the field of pharmacy, relates to novel medicinal application of hydrogen sulfide and a donor thereof sodium hydrosulfide to pharmacy, and in particular relates to application of hydrogen sulfide and donor thereof sodium hydrosulfide to preparation of medicament for treating diabetes. The invention adopts the exogenous hydrogen sulfide and its donor sodium hydrosulfide (NaHS) for insulin sensibilization and tests for regulating blood sugar level and increasing insulin level for type II diabetes. Through correlation test of skeletal muscle and adipose cells with insulin resistance, insulin tolerance test by using animal model for diabetes insulin resistance, glucose consumption experiment, animal model experiment for diabetes insulin resistance and NaHS intervention animal experiment, the results show that NaHS can promote glucose uptake in the presence of insulin, thus indicating insulin enhancement effect. The invention of hydrogen sulfide and the donor thereof sodium hydrosulfide can be used as insulin sensitizers and medicaments for regulating blood sugar level and increasing insulin level for type II diabetes.
Description
Technical field
The invention belongs to medicine pharmaceutical field, relate to hydrogen sulfide and donor sodium hydrosulfide thereof new pharmaceutical usage in pharmacy, relate in particular to hydrogen sulfide and donor sodium hydrosulfide thereof the purposes in preparation treatment diabetes medicament.Hydrogen sulfide of the present invention and donor sodium hydrosulfide thereof can be used as euglycemic agent and to type Ⅱdiabetes mellitus blood sugar lowering and increase the medicine of insulin level.
Background technology
Prior art discloses hydrogen sulfide (H
2s) be the metabolite of cysteine in human body, its content in human body is very low is about 20～50 μ mol/L, and is difficult for manual control, and document is also reported H
2s is a kind of novel endogenous gas molecule that participates in cardiovascular activity, has the purposes that promotes cardiovascular disease angiogenesis.
Statistics report, at present, diabetes are 1-2% at population of China sickness rate, can be up to 12% in old people.The diabetes diagnosis standard of revising according to international diabetologist committee, diagnosis standards of fasting plasma glucose is >=126mg/ml, the sickness rate of diabetes is ascendant trend year by year, and the patient of type 2 diabetes mellitus (great majority are senile diabetes) significantly increases, and to the harm of human health, also will be larger.
At present, the clinical treatment to type 2 diabetes mellitus, generally adopt diet in conjunction with hypoglycemic drug as basic skills.Oral hypoglycemic owner will use western medicine, and still, practice shows, Western medicine all has adverse side effect to the cardiovascular of diabetic and liver, kidney etc., and should not use for multiple complications person.For many years, endocrine, diabetologist, scholar treat the whole bag of tricks and the medicine of diabetes from all many-sided discussions both at home and abroad.People expect have new medicine safer, effective and that have no side effect to come out early.
Summary of the invention
Object of the present invention is to provide hydrogen sulfide (H
2s) and the new purposes of donor sodium hydrosulfide (NaHS) in pharmacy.Relate in particular to hydrogen sulfide and donor sodium hydrosulfide thereof the purposes in preparation treatment diabetes medicament.Hydrogen sulfide of the present invention and donor sodium hydrosulfide thereof can be used as euglycemic agent and to type Ⅱdiabetes mellitus blood sugar lowering and increase the medicine of insulin level.
The present invention adopts exogenous hydrogen sulfide and donor sodium hydrosulfide NaHS thereof for insulin sensitivity enhancing with to type Ⅱdiabetes mellitus blood sugar lowering and the test of increasing insulin level, comprise: the correlation test of skeletal muscle and adipose cell and insulin resistant, the animal model of diabetes insulin opposing carries out insulin tolerance experiment, glucose consumption experiment, the animal model test of diabetes insulin opposing and give NaHS and intervene zoopery etc., result shows: NaHS can play the effect that promotes glucose uptake in the situation that insulin exists, prompting NaHS can strengthen the effect of insulin, hydrogen sulfide and donor sodium hydrosulfide thereof can be used as euglycemic agent,
By the correlation test of skeletal muscle and adipose cell and insulin resistant, result confirms, NaHS significantly increases skeletal muscle under insulin stimulating and the metabolism of adipose cell glucose within the scope of to the substantially nontoxic safe concentration of cultured cell;
The animal model of resisting by diabetes insulin carries out insulin tolerance experiment, and result shows low dose of H
2s can increase the insulin sensitivity of GK rat;
By glucose consumption experimental result, confirm, NaHS significantly increases skeletal muscle under insulin stimulating and the metabolism of adipose cell glucose within the scope of to the substantially nontoxic safe concentration of cultured cell; Hydrogen sulfide glucose uptake normal for adipose cell and model cell base state has facilitation, but does not affect for the glucose uptake of Skeletal Muscle Cell base state;
The animal model test of resisting by diabetes insulin, result demonstration, hydrogen sulfide and donor sodium hydrosulfide thereof have blood sugar lowering and insulin-sensitizing effect to type Ⅱdiabetes mellitus, can increase insulin level;
By chronic, give NaHS zoopery; result shows; the chronic NaHS of giving can reduce the expression of ROS in GK rat kidney and can reduce the numbers of glomeruli that crescent pathological changes occurs in GK rat kidney; show that the kidney injury that hydrogen sulfide and donor sodium hydrosulfide thereof cause diabetes has protective effect; there is the effect that control diabetogenous nephrosis disease of ZANG-organs is frozen, can also reduce the oxidative stress of kidney.
The results show; hydrogen sulfide of the present invention and donor sodium hydrosulfide NaHS thereof can be used as euglycemic agent; with by blood sugar lowering and insulin-sensitizing effect; can increase insulin level; as treatment type Ⅱdiabetes mellitus medicine; the kidney injury that described hydrogen sulfide and donor sodium hydrosulfide thereof cause diabetes has protective effect, can prevent and treat the effect that diabetogenous nephrosis disease of ZANG-organs is frozen, and can also reduce the oxidative stress of kidney.
H of the present invention
2the advantage of S and donor NaHS thereof has:
1, hydrogen sulfide and donor sodium hydrosulfide thereof can be used as euglycemic agent;
2, hydrogen sulfide and donor sodium hydrosulfide thereof have blood sugar lowering and insulin-sensitizing effect to type Ⅱdiabetes mellitus, can increase insulin level;
3, the kidney injury that hydrogen sulfide and donor sodium hydrosulfide thereof cause diabetes has protective effect, has the effect that control diabetogenous nephrosis disease of ZANG-organs is frozen, and can also reduce the oxidative stress of kidney.
Accompanying drawing explanation
Fig. 1. the NaHS(0-200 μ mol/L of variable concentrations) hatch Skeletal Muscle Cell after 24 hours, the impact on glucose uptake under insulin stimulating state.
Fig. 2. the NaHS(0-200 μ mol/L of variable concentrations) hatch adipose cell after 24 hours, the impact on glucose uptake under insulin stimulating state.
Fig. 3. the NaHS(0-200 μ mol/L of variable concentrations) Skeletal Muscle Cell after 24 hours of hatching insulin resistant, the impact on glucose uptake under insulin stimulating state.
Fig. 4. the NaHS(0-200 μ mol/L of variable concentrations) adipose cell after 24 hours of hatching insulin resistant, the impact on glucose uptake under insulin stimulating state.
Fig. 5. matched group and NaHS(50 μ mol/L) low sugar (5.5mmol/L) Skeletal Muscle Cell after 24 hours of hatching insulin resistant, the impact on glucose uptake under insulin of different concentration (0-100nmol/L) stimulation state.
Fig. 6. matched group and NaHS(50 μ mol/L) low sugar (5.5mmol/L) adipose cell after 24 hours of hatching insulin resistant, the impact on glucose uptake under insulin of different concentration (0-100nmol/L) stimulation state.
Fig. 7. matched group and NaHS(50 μ mol/L) high sugar (25mmol/L) Skeletal Muscle Cell after 24 hours of hatching insulin resistant, the impact on glucose uptake under insulin of different concentration (0-100nmol/L) stimulation state.
Fig. 8. matched group and NaHS(50 μ mol/L) high sugar (25mmol/L) adipose cell after 24 hours of hatching insulin resistant, the impact on glucose uptake under insulin of different concentration (0-100nmol/L) stimulation state.
Fig. 9. after lumbar injection insulin (0.75U/kg), the time changing curve of GK rat blood sugar.
Figure 10. after lumbar injection insulin (0.75U/kg), the time changing curve of Wistar rat blood sugar.
Figure 11. after lumbar injection insulin (0.40U/kg), the time changing curve of Wistar rat blood sugar.
Figure 12 .NaHS administration is GK rat and the variation of Wistar rat chronic fasting glucose during 10 weeks.
The administration of Figure 13 .GK rat chronic is carbohydrate tolerance experiment after 8 weeks
The administration of Figure 14 .Wistar rat chronic is carbohydrate tolerance experiment after 8 weeks
The administration of Figure 15 .GK rat chronic is insulin level after 8 weeks
Figure 16. chronic administration is after 10 weeks, and in the kidney of GK rat, ROS expresses and occur the numbers of glomeruli of crescent pathological changes.
The specific embodiment
The NaHS(1-200 μ mol/L of variable concentrations) hatch after 24 hours, for not impact of the glucose uptake under normal Skeletal Muscle Cell base state, whether detected NaHS in the situation that insulin exists acts on for Skeletal Muscle Cell glucose uptake, the Skeletal Muscle Cell of the NaHS(0-200 μ mol/L of detection variable concentrations) hatching glucose (5.5 μ mol/L) and insulin (100nmol/L) opposing is after 24 hours, impact on glucose uptake under insulin stimulating state, result shows (as shown in Figure 1), NaHS is 25, the concentration of 50 and 100 μ mol/L all significantly increases
3the picked-up of H-deoxyglucose, NaHS promotes that the optium concentration of glucose uptake is 100 μ mol/L, compare with matched group and increase over 1 times, be 2.06 ± 0.29(P < 0.01), the NaHS of 25 and 50 μ mol/L increases respectively glucose uptake rate to 1.54 ± 0.08 and 1.72 ± 0.32, result shows that NaHS can play the effect that promotes glucose uptake in the situation that insulin exists, and prompting NaHS can strengthen the effect of insulin, i.e. insulin-sensitizing effect,
The NaHS of variable concentrations, hatches 24 hours from (0-200 μ mol/L), and for not impact of the glucose uptake under normal adipose cell insulin stimulating state, prompting NaHS works and may not pass through insulin for the glucose uptake of adipose cell; The NaHS of variable concentrations, from (0-200 μ mol/L), hatch 24 hours, carry out glucose uptake experiment, result shows (as shown in Figure 2), hydrogen sulfide has obvious facilitation for the glucose uptake under normal adipose cell insulin existence, and NaHS all significantly increases in the concentration of 25,50 and 100 μ mol/L
3h-deoxyglucose picked-up, different from Skeletal Muscle Cell, NaHS promotes that the optium concentration of adipose cell glucose uptake is 50 μ mol/L, is 1.54 times of matched group;
Result shows, the role of fatty tissue in glucose transport is much smaller than skeletal muscle tissue, and skeletal muscle tissue participates in 75% of whole body glucose uptake, the caused adipose cell of NaHS valid density
3the amplitude of the increase of H-deoxyglucose picked-up is much smaller than Skeletal Muscle Cell.
Insulin sensitivity is badly damaged in type Ⅱdiabetes mellitus, glucose uptake when we observe sulfuration Hydrogen Energy and increase insulin and exist in normal skeletal myoblast, but on the not impact of the glucose uptake of base state.We may have certain insulin-sensitizing effect by hydrogen sulfide this results suggest.
During according to diabetes in Patients with Insulin Resistance body ubiquity hyperinsulinism or/and the pathological characteristic of hyperglycemia, in the present embodiment, according to pertinent literature, report, on the basis of normal cultivation Skeletal Muscle Cell, with the environmental induction of the high sugar of high concentration insulin, cultivate Skeletal Muscle Cell, set up the cell model (IR model) of insulin resistant, and pass through
3h-deoxyglucose picked-up test is identified, detects the effect of hydrogen sulfide to the glucose uptake of the cell of insulin resistant under base state and insulin stimulating state.
Comprising,
Set up the cell model of insulin resistant, using model group (IR) glucose uptake amount as picked-up base value, each organizes respectively the glucose uptake rate separately of conduct by comparison, result shows, NaHS is hatched the basic glucose uptake for IR model Skeletal Muscle Cell after 24 hours not to be affected, this is consistent with the result of normal cell base state, and prompting NaHS works and depends on the existence of insulin;
Further research exists in situation NaHS for the effect of the grape cell Sugar intake of IR model at insulin, and result shows,
Insulin stimulating (100nmol/L) in the situation that, NaHS all significantly increases IR model L6 cell in the concentration of 25,50 and 100 μ mol/L
3h-deoxyglucose picked-up (as shown in Figure 3), wherein the NaHS of 50 and 100 μ mol/L is close for the effect of IR cell, and the increase degree of the glucose uptake that NaHS valid density causes in IR model cell is significantly less than normal cell, 25, the NaHS of 50 and 100 μ mol/L increases respectively glucose uptake to 1.61 ± 0.57,1.72 ± 0.53 and 1.56 ± 0.36 times, illustrates that NaHS can play the effect that promotes glucose uptake under pathological state;
The NaHS of variable concentrations, from 0-200 μ mol/L, hatch 24 hours, for not impact of the glucose uptake under normal adipose cell insulin stimulating state, the NaHS of 25 μ mol/L compared with the control, glucose uptake rate has increase, and prompting NaHS works and may not pass through insulin for the glucose uptake of adipose cell;
The NaHS of variable concentrations, from 0-200 μ mol/L, hatch 24 hours, carry out glucose uptake experiment, hydrogen sulfide has obvious facilitation for the glucose uptake under normal adipose cell insulin existence, and NaHS all significantly increases in the concentration of 25,50 and 100 μ mol/L
3h-deoxyglucose picked-up, different from Skeletal Muscle Cell, NaHS promotes that the optium concentration of adipose cell glucose uptake is 50 μ mol/L, is 1.54 times of matched group;
The NaHS of variable concentrations, hatches 24 hours from 0-200 μ mol/L, and for not impact of the glucose uptake under IR model adipose cell insulin stimulating state, compared with the control, glucose uptake rate slightly increases by the NaHS of 50 μ mol/L;
Cell cultivates through the sugared hyperinsulinism combined induction of height the cell model of setting up insulin resistant, using model group (IR) glucose uptake amount as picked-up base value, each organizes respectively the glucose uptake rate (as shown in Figure 4) separately of conduct by comparison, NaHS was hatched after 24 hours has facilitation for the glucose uptake under the adipose cell insulin stimulating of IR model, consistent with the result of normal adipose cell, NaHS promotes that the optium concentration of IR model adipose cell glucose uptake is 50 μ mol/L, for 2.02 ± 0.86 times of matched group, the NaHS of 25 and 100 μ mol/L is increased to 1.75 ± 0.68 and 1.56 ± 0.44 times.
In the present embodiment, detected the impact of hydrogen sulfide on glucose uptake under insulin of different concentration (0-100nmol/L) stimulation state, result demonstration,
Matched group and NaHS(50 μ mol/L) processed group low sugar (5.5mmol/L) hatches the Skeletal Muscle Cell (as shown in Figure 5) of insulin resistant and adipose cell after (as shown in Figure 6) 24 hours, insulin concentration is 10 and during 100nmol/L, NaHS processed group compared with the control, glucose uptake is significantly increased, wherein 0,1 and during 5nmol/L without significant difference;
Matched group and NaHS(50 μ mol/L) the high sugar of processed group (25mmol/L) hatches the Skeletal Muscle Cell (as shown in Figure 7) of insulin resistant and adipose cell after (as shown in Figure 8) 24 hours, insulin concentration is 10 and during 100nmol/L, NaHS processed group compared with the control, glucose uptake is significantly increased, wherein 0,1 and during 5nmol/L without significant difference;
The correlation test of embodiment 2 skeletal muscle and adipose cell and insulin resistant
In the present embodiment, adopt insulin resistant and the diabetes cell of extensive use in prior art: wherein, skeletal myoblast strain is Yaffe separated obtaining from the primary culture of rat thigh flesh, can merge the myotube and the rhabdium that form multinuclear under certain condition of culture; Adipose cell strain derives from mouse embryo fibroblasts, through clonal expansion, becomes pre-adipose cell lines, then is induced to differentiate into mature fat cell through specific differentiation agent;
1) evaluation of cellular level insulin sensitivity
Utilize cell to test isotope-labeled glucose uptake, evaluate cell to the glucose uptake of insulin stimulating and utilize ability, thereby evaluating the sensitivity of insulin, judge whether insulin resistant exists;
Glucose consumption experiment: the amount of processing the sugared concentration calculating sugar consumption in culture medium after 24 hours by mensurations, pass judgment on the ability of cellular uptake sugar, glucose metabolism situation with reflection cell, therefore, the present embodiment is the impact on the insulin sensitivity of Skeletal Muscle Cell and adipose cell in conjunction with the result overall merit hydrogen sulfide of glucose consumption and glucose uptake, wherein, comprise the effect of hydrogen sulfide to the glucose uptake of Skeletal Muscle Cell and adipose cell under physiology and pathological state;
(1) set up insulin resistant cell model
By the method for the sugared hyperinsulinism of height, set up insulin resistant cell model, pathology environment with hyperglycemia hyperinsulinemia in simulation Patients with Insulin Resistance body, wherein, the adipose cell of differentiation and Skeletal Muscle Cell myotube adopt high concentration insulin and high sugared inducing culture 24h, then with
3the picked-up of H-deoxyglucose is verified;
In experiment, with mtt assay, monitor the impact on adipose cell and Skeletal Muscle Cell vigor when the variable concentrations of each effective ingredient, result shows, when NaHS concentration is 10 to 200 μ mol/L, cell viability is had no significant effect, concentration has certain toxicity to cell after being greater than 500 μ mol/L, and the present embodiment determines that it is 10 to 200 μ mol/L that glucose consumption afterwards and glucose uptake are tested concentration used.
Glucose consumption experimental result confirms, NaHS significantly increases skeletal muscle under insulin stimulating and the metabolism of adipose cell glucose within the scope of to the substantially nontoxic safe concentration of cultured cell;
Normal and insulin resistant model cell
3h-deoxyglucose picked-up result of the test shows, model cell glucose uptake ability basis with under insulin stimulating state, compared obvious decline with normal cell, high concentration glucose high concentration insulin can obviously suppress the picked-up of glucose;
The demonstration of pharmaceutical intervention result, hydrogen sulfide glucose uptake normal for adipose cell and model cell base state all has facilitation, but does not affect for the glucose uptake of Skeletal Muscle Cell base state; When insulin exists, NaHS can significantly increase the glucose uptake of adipose cell and Skeletal Muscle Cell, and this acting in normal and insulin resistant model cell all exists; Results suggest, hydrogen sulfide may be different to the mechanism of action of Skeletal Muscle Cell and adipose cell.
Embodiment 3 hydrogen sulfide and donor sodium hydrosulfide thereof are to the blood sugar lowering of type Ⅱdiabetes mellitus and insulin-sensitizing effect
Select the GK rat at 2 monthly ages as the animal model of the present embodiment diabetes insulin opposing;
Routine is carried out insulin tolerance test, experimental result shows, after a certain amount of insulin of rats by intraperitoneal injection of chronic administration 60 minutes, the ratio that the blood glucose of GK rat NaHS 30 μ mol/kg groups declines is obviously greater than matched group (as shown in Figure 9), and the ratio that the blood glucose of Wistar rat NaHS 60 μ mol/kg groups declines is obviously greater than matched group (as shown in figure 10); Insulin sensitivity experiment, the hungry 4 hours Wistar rats of insulin (0.4U/kg) of employing low concentration, NaHS 60 μ mol/kg groups relatively have obvious decline (as shown in figure 11) with matched group, and result shows, low dose of H
2s can increase the insulin sensitivity of GK rat;
After NaHS administration, within 2,4,6 weeks, detect respectively the fasting glucose content (as shown in figure 12) of GK diabetes rat, administration is low dose of NaHS(30 μ mol/kg after 4 weeks) show hypoglycemic effect, compared significant difference with matched group, show low concentration H
2s can reduce the fasting glucose of GK diabetes rat.
Carbohydrate tolerance test shows that the blood glucose of respectively organizing GK rat each time point after glucose load is all significantly higher than Wistar group, GK rat impaired glucose tolerance (as shown in figure 13) is described, when lumbar injection glucose 30 minutes and 90 minutes, the blood sugar concentration of the rat of NaHS administration low dose group is starkly lower than matched group; After glucose load, the blood glucose value of 30 and 90 minutes NaHS 30 μ mol/kg groups, than the remarkable reduction of matched group, illustrates that NaHS increases carbohydrate tolerance;
Lumbar injection glucose in the time of 30 minutes NaHS low dose group (30 and 60 μ mol/kg) and matched group blood glucose value there is significant difference (as shown in figure 14), lumbar injection glucose in the time of 60 minutes NaHS 60 μ mol/kg groups there is significant difference with matched group blood glucose value, show H
2s is influential to the glucose tolerance of Wistar rat diabetes;
Low concentration NaHS(30 μ mol/kg/d) can improve the insulin resistant of GK rat, reduce fasting glucose (FBG), increase glucose tolerance, heavy dose of NaHS(120 μ mol/kg/d) increased the weight of the insulin resistant of GK rat, fasting glucose raises, impaired glucose tolerance, result shows H
2s has dual regulation effect for the insulin resistant in body.
The protective effect of the kidney injury that embodiment 4 hydrogen sulfide and donor sodium hydrosulfide thereof cause diabetes
The chronic NaHS variable concentrations (30,60 and 120 μ mol/L) that gives, after 10 weeks, is observed the expression of ROS in GK rat kidney according to a conventional method, and result shows (as shown in Figure 16 A): in GK rat matched group kidney, ROS expresses apparently higher than Wistar rat; GK rat medication group and the comparison of GK rat matched group, NaHS variable concentrations (30,60 and 120 μ mol/L) all can obviously reduce the expression of ROS in kidney, and becomes certain concentration dependent (as shown in Figure 16 C4);
The chronic NaHS variable concentrations (30 that gives, 60 and 120 μ mol/L) after 10 weeks, kidney section, with PAS, dye, result shows, GK rat matched group is compared the extracellular matrix severe hypertrophy of glomerule with Wistar rat, form tuberous sclerosis, being concentric circles arranges, be Kimmelstiel-Wilson tuberosity (Kimmelstie l-Wilson nodule), give NaHS variable concentrations (30, 60 and 120 μ mol/L) after 10 weeks (as shown in Figure 16 B and D), the numbers of glomeruli of hypertrophy and the obvious minimizing of GK matched group, show that the chronic NaHS of giving can reduce the numbers of glomeruli that crescent pathological changes occurs in GK rat kidney, the kidney injury that hydrogen sulfide and donor sodium hydrosulfide thereof cause diabetes has protective effect.
Claims (7)
1. hydrogen sulfide and donor sodium hydrosulfide thereof are treated the purposes in diabetes medicament in preparation.
2. by purposes claimed in claim 1, wherein said diabetes are type Ⅱdiabetes mellitus.
3. by the purposes described in claim 1 or 2, wherein hydrogen sulfide and donor sodium hydrosulfide thereof are used for type Ⅱdiabetes mellitus blood sugar lowering and increase insulin level.
4. hydrogen sulfide and donor sodium hydrosulfide thereof the purposes in preparing euglycemic agent.
5. hydrogen sulfide and donor sodium hydrosulfide thereof are prevented and treated the purposes in the kidney injury medicine that diabetes cause in preparation.
6. by purposes claimed in claim 5, the kidney injury that wherein said diabetes cause is the renal complication that type Ⅱdiabetes mellitus causes.
7. by purposes claimed in claim 5, wherein hydrogen sulfide and donor sodium hydrosulfide thereof are for reducing the oxidative stress of kidney.
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Cited By (5)
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| CN104496782A (en) * | 2014-12-05 | 2015-04-08 | 吉林大学 | Perfluorooctane-based compound and method for preparing perfluorooctane-containing terminated polyaryl ether sulphone |
| CN106176801A (en) * | 2015-05-06 | 2016-12-07 | 复旦大学 | Hydrogen sulfide purposes in struvite anemia medicine is treated in preparation |
| CN106539818A (en) * | 2015-09-20 | 2017-03-29 | 复旦大学 | Hydrogen sulfide and its donor sodium hydrosulfide are preparing the purposes promoted in hemopoietic medicine |
| IT202000009700A1 (en) | 2020-05-04 | 2021-11-04 | Parthenogen Sagl | COMBINATION OF MICRONUTRIENTS TO STIMULATE THE ENDOGENOUS PRODUCTION OF HYDROGEN SULFIDE (H2S) |
| CN113801841A (en) * | 2020-06-12 | 2021-12-17 | 温州医科大学 | Method for detecting insulin sensitivity of AdipoRon to mouse skeletal muscle cells |
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Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104496782A (en) * | 2014-12-05 | 2015-04-08 | 吉林大学 | Perfluorooctane-based compound and method for preparing perfluorooctane-containing terminated polyaryl ether sulphone |
| CN106176801A (en) * | 2015-05-06 | 2016-12-07 | 复旦大学 | Hydrogen sulfide purposes in struvite anemia medicine is treated in preparation |
| CN106176801B (en) * | 2015-05-06 | 2020-06-09 | 复旦大学 | Application of hydrogen sulfide in preparation of medicine for treating inflammatory anemia |
| CN106539818A (en) * | 2015-09-20 | 2017-03-29 | 复旦大学 | Hydrogen sulfide and its donor sodium hydrosulfide are preparing the purposes promoted in hemopoietic medicine |
| IT202000009700A1 (en) | 2020-05-04 | 2021-11-04 | Parthenogen Sagl | COMBINATION OF MICRONUTRIENTS TO STIMULATE THE ENDOGENOUS PRODUCTION OF HYDROGEN SULFIDE (H2S) |
| WO2021224153A1 (en) | 2020-05-04 | 2021-11-11 | Parthenogen Sagl | Combination of micronutrients to stimulate the endogenous production of hydrogen sulfide (h2s) |
| CN113801841A (en) * | 2020-06-12 | 2021-12-17 | 温州医科大学 | Method for detecting insulin sensitivity of AdipoRon to mouse skeletal muscle cells |
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| CN103622992B (en) | 2017-06-13 |
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