CN106177917A - A kind of insulin aspart injection and preparation method thereof - Google Patents
A kind of insulin aspart injection and preparation method thereof Download PDFInfo
- Publication number
- CN106177917A CN106177917A CN201610736379.1A CN201610736379A CN106177917A CN 106177917 A CN106177917 A CN 106177917A CN 201610736379 A CN201610736379 A CN 201610736379A CN 106177917 A CN106177917 A CN 106177917A
- Authority
- CN
- China
- Prior art keywords
- injection
- insulin aspart
- insulin
- mannatide
- concentration
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/22—Hormones
- A61K38/28—Insulins
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/02—Inorganic compounds
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/08—Solutions
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Engineering & Computer Science (AREA)
- Gastroenterology & Hepatology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Immunology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Dermatology (AREA)
- Inorganic Chemistry (AREA)
- Diabetes (AREA)
- Endocrinology (AREA)
- Zoology (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Abstract
The invention provides a kind of insulin aspart injection and preparation method thereof, containing insulin aspart, α mannatide, zinc salt and antibacterial in this injection, the insulin aspart therein concentration in injection is 300 1200nmol/mL, and α mannatide concentration in injection is 10 100nmol/mL.Insulin resistant can be improved, improve the target tissue sensitivity to insulin, it is possible not only to reduce dosage and reaches expection treatment index, and it is not result in the toxic and side effects such as hypoglycemia, edema, allergy, significantly reduce toxicity and the probability of drug resistance occurs, reducing medical expense.
Description
Technical field
The invention belongs to technical field of medicine, in particular to a kind of insulin preparation, particularly relate to one and contain
Injection having insulin aspart and preparation method thereof.
Background technology
At present, the whole world has more than the diabetics of 3. 82 hundred million, and wherein China's diabetics of more than 18 years old is about
Have 1.14 hundred million.All the time, insulin is all the treatment maximally effective medicine of diabetes, but when regular insulin also exists effect
Between short, absorb that variation is big, the effect problems such as peak value is obvious, hypoglycemic incidence is high, the most day by day by insulin analog institute
Substitute (Cao Fenglin, Deng Shaoxiong. insulin analog: the newly selected (J) for the treatment of diabetes. Medical review, 2007,1 (13)
: 32-34.).Restructuring insulin aspart, as a kind of Insulin Asp, is to utilize genetic engineering DNA recombinant technique
(Warren ML, Conway MJ, Klaff LJ, et al. Postprandial versus preprandial dosing
of biphasic insulin aspart in elderly type 2 diabetes patients〔J〕. Diabetes
Res ClinPract, 2004,66 (11): 23-29.) proline (Pro) of the 28th, insulin human B chain is replaced
For the Aspartic Acid (Asp) of negative charge, utilize the repulsive interaction of electric charge to stop insulin monomer or dimeric oneself to be gathered
Close, make intermolecular polymerization reduce.It not only can simulate the secretion pattern of insulin human well, controls hypoglycemic effect preferable,
And due to the shortening of its acting duration, be difficult to under before the meal or insulin action at night superposes, substantially reduce
Hypoglycemic incidence rate.Although insulin is the choice drug for the treatment of diabetes, but there is a lot of shortcoming, as a long time the most simultaneously
Use problems such as producing insulin resistant.
Summary of the invention
In view of insulin aspart is easily generated the problem of insulin resistant in life-time service, it is an object of the invention to provide
A kind of insulin aspart injection improving insulin resistant and preparation method thereof.
In order to realize the purpose of the present invention, inventor passes through lot of experiments persistent exploration, is finally obtained one
Insulin aspart injection, containing insulin aspart, α-mannatide, zinc salt and antibacterial, door therein in this injection
Winter insulin concentration in injection is 300-1200nmol/mL, and α-mannatide concentration in injection is 10-
100nmol /mL。
In order to preferably test the purpose of the present invention, the technical parameter of above-mentioned insulin aspart injection is done by inventor
The most preferred, particularly as follows:
Insulin aspart injection as above, the insulin aspart therein concentration in injection is 500-800nmol/
ML, α-mannatide concentration in injection is 20-50nmol/mL.
The most preferably, insulin aspart injection as above, in this injection, insulin aspart is in injection
Concentration in liquid is 600nmol/mL, and α-mannatide concentration in injection is 30nmol/mL, and uses pH adjusting agent
Tune pH value is 4.0-4.2.
The most preferably, insulin aspart injection as above, antibacterial therein is metacresol, described
Zinc salt is zinc chloride.
It addition, present invention also offers the preparation method of a kind of insulin aspart injection, the method comprises the steps:
(1) α-mannatide is joined in the water for injection of 30-80% full dose and is stirred to dissolve, regulate pH to 4.0-4.2,
Add insulin aspart and stirring makes it dissolve, standby；
(2) zinc salt and antibacterial are joined in the water for injection of surplus, be stirred to dissolve, standby；
(3) solution that step (1) is prepared is joined in the solution that step (2) is prepared under agitation, mix homogeneously, regulation
Medicinal liquid pH value, to 4.0-4.2, filtration sterilization, fill, obtains insulin aspart injection.
In the preparation method of above-mentioned insulin aspart injection, described pH adjusting agent is 0.1mol/L hydrochloric acid；If
During condition pH, hydrochloric acid dropping too much causes pH to be less than desired value, then can heighten with 0.1mol/L sodium hydroxide solution.
The synergism of insulin resistant is improved, the therefore present invention in view of α-mannatide combination insulin aspart has
Also provide for a kind of new pharmaceutical use, it may be assumed that α-mannatide drops in preparation with the active ingredient compositions of insulin aspart composition
Application in hypoglycemic medicament.The most described medicine is injection.
Compared with prior art, the insulin aspart injection that the present invention relates to can improve insulin resistant, improve target group
Knit the sensitivity to insulin, be possible not only to reduce dosage and reach expection treatment index, and be not result in hypoglycemia, water
The toxic and side effects such as swollen, allergy, significantly reduce toxicity and the probability of drug resistance occur, reducing medical expense, clinical in diabetes
Application aspect has the biggest potentiality, brings new hope to diabetics.It addition, the preparation technology letter of injection of the present invention
Single, it is easy to industrialized great production.
Accompanying drawing explanation
Fig. 1 is HepG2 insulin resistant cell model glucose absorption rate under different tested material effect；
Wherein: 1, blank group；2,0.1nmol/L insulin aspart；3,1nmol/L insulin aspart；4,10nmol/L door
Winter insulin；5,100nmol/L insulin aspart；6,1000nmol/L insulin aspart；7,10nmol/L α-mannatide；
8,0.1nmol/L insulin aspart+10nmol/L α-mannatide；9,1nmol/L insulin aspart+10nmol/L α-manna
Polysaccharide peptide；10,10nmol/L insulin aspart+10nmol/L α-mannatide；11,100nmol/L insulin aspart+
10nmol/L α-mannatide；12,1000nmol/L insulin aspart+10nmol/L α-mannatide.
Detailed description of the invention
In order to make present disclosure be more likely to be clearly understood, below according to the specific embodiment of the present invention and combine
Accompanying drawing, the present invention is further detailed explanation, advantages of the present invention and feature will be with describe and apparent.But
It should be understood that following example are only exemplary, protection scope of the present invention is not constituted any restriction.Those skilled in the art
It should be understood that and the details of technical scheme and form can be modified or replace without departing from the spirit of the invention,
But these amendments or replacement each fall within protection scope of the present invention.
The preparation of embodiment 1 insulin aspart injection
Insulin aspart 1.2mmol
α-mannatide 0.03mmol
Metacresol 2500mg
Zinc chloride 28mg
Water for injection adds to 1000mL
Preparation technology:
(1) α-mannatide is joined in 750mL water for injection it is stirred to dissolve, regulate pH with 0.1mol/L hydrochloric acid solution
To 4.0-4.2, add recipe quantity insulin aspart and stirring makes it dissolve, standby；
(2) zinc salt and metacresol are joined in the water for injection of surplus, be stirred to dissolve, standby；
(3) solution that step (1) is prepared is joined in the solution that step (2) is prepared under agitation, mix homogeneously, add
0.1mol/L hydrochloric acid solution regulation medicinal liquid pH value is to 4.0-4.2, and 0.22 μm membrane filtration is degerming, fill, obtains insulin aspart note
Penetrate liquid.
The preparation of embodiment 2 insulin aspart injection
Insulin aspart 0.6mmol
α-mannatide 0.03mmol
Metacresol 2500mg
Zinc chloride 28mg
Water for injection adds to 1000mL
Preparation technology:
(1) α-mannatide is joined in 700mL water for injection it is stirred to dissolve, regulate pH with 0.1mol/L hydrochloric acid solution
To 4.0-4.2, add recipe quantity insulin aspart and stirring makes it dissolve, standby；
(2) zinc salt and metacresol are joined in the water for injection of surplus, be stirred to dissolve, standby；
(3) solution that step (1) is prepared is joined in the solution that step (2) is prepared under agitation, mix homogeneously, add
0.1mol/L hydrochloric acid solution regulation medicinal liquid pH value is to 4.0-4.2, and 0.22 μm membrane filtration is degerming, fill, obtains insulin aspart note
Penetrate liquid.
The preparation of embodiment 3 insulin aspart injection
Insulin aspart 0.3mmol
α-mannatide 0.03mmol
Metacresol 2500mg
Zinc chloride 28mg
Water for injection adds to 1000mL
Preparation technology:
(1) α-mannatide is joined in 700mL water for injection it is stirred to dissolve, regulate pH with 0.1mol/L hydrochloric acid solution
To 4.0-4.2, add recipe quantity insulin aspart and stirring makes it dissolve, standby；
(2) zinc salt and metacresol are joined in the water for injection of surplus, be stirred to dissolve, standby；
(3) solution that step (1) is prepared is joined in the solution that step (2) is prepared under agitation, mix homogeneously, add
0.1mol/L hydrochloric acid solution regulation medicinal liquid pH value is to 4.0-4.2, and 0.22 μm membrane filtration is degerming, fill, obtains insulin aspart note
Penetrate liquid.
The foundation of embodiment 4 HepG2 cell insulin resistant model
Take the logarithm the HepG2 cell of trophophase, be inoculated in 96 orifice plates, add the DMEM culture medium containing 10% new-born calf serum,
37℃、5%CO2, cultivate under the conditions of saturated humidity.After cell attachment, wash 2 with the DMEM culture fluid without calf serum
Secondary, that add that 200 μ L newly prepare 1 × 10−7mol·L−1Biosynthetic human insulin, in 37 DEG C, 5% CO2Incubator is hatched 24h,
Make cell that the biological effect of insulin is produced opposing, the matched group being not added with insulin is set simultaneously.
Embodiment 5 insulin resistant HepG2 cell model is identified
The DMEM culture fluid that the cell of model group and the normal group cell that processes without insulin add without calf serum is washed
2 times, then be separately added into containing 1000,100,10,1 and 0.1nmol L−1Insulin human or the culture medium without insulin human, in
37℃、5%CO2Under the conditions of continue to hatch 24h.Culture fluid is detected by glucoseoxidase peroxidase (GOD-POD) method
The glucose content of middle residual, subtracts each other with the glucose content average in the multiple hole of non-inoculating cell blank, calculates the Portugal of each porocyte
Grape sugar consumption rate, determines that according to the glucose uptake amount of cell the structure of insulin resistant cell model is the most successful.
Calculate the concentration of the glucose of residual, formula: concentration of glucose (mmol L in culture fluid−1)=A Sample/A Standard×
5.55mmol·L−1；Calculate the cell consumption rate to glucose, formula: grape cell sugar consumption rate (%)=[(C Blank glucose −C It is administered glucose)/C Blank glucose]×100%。
Result of the test shows: the cell after the process of high concentration insulin and the glucose consumption of the normal compared with control cells cultivated
Rate all raises along with the rising of insulin concentration, in dose-dependent relationship, but more than 10nmol L−1High concentration islets of langerhans
Element process after grape cell sugar consumption rate cultivate significantly lower than normal cell (P<0.01).After this explanation insulin processes,
HepG2 cells show goes out insulin resistant, shows that insulin can not play it well and promote target cell consumption of glucose
Effect, thus explanation utilizes high concentration insulin process HepG2 to be successfully established HepG2 cell insulin resistant model.
The experimental study to HepG2 insulin resistant cell model glucose absorption of embodiment 6 tested material
Insulin aspart is diluted so that it is final concentration is 0.1,1,10,100 and 1000 nmol L with serum-free medium−1。
α-mannatide is diluted so that it is final concentration is 10nmol L with serum-free medium−1.Take HepG2 insulin resistant cell
Model, choose successively concentration be 0,10nmol L−1α-mannatide respectively with 0,0.1,1,10,100,1000nmol L−1Insulin aspart common function cells model.After continuing to cultivate 24h, detect different disposal group grape cell sugar absorbance, each
Concentration at least sets 3 independent repeating holes, calculates the cell consumption rate to glucose.
Result of the test shows: α-mannatide or (with) the insulin aspart effect HepG2 islets of langerhans of variable concentrations
After element opposing cell model, using GOD-POD method detection cell sugar absorbance, result is as shown in Figure 1.Insulin aspart is individually located
Reason cell model glucose absorption rate is low, though maximum dose level (1000nmol L−1) the glucose absorption rate that processes is only
(12.5 ± 0.8) %, and along with the reduction of dosage, grape cell sugar absorbance is gradually reduced, 0.1 nmol L−1Insulin aspart
The sugared absorbance of process group cell model without significant difference (P ＞ 0.05), illustrates 0.1 nmol L compared with model control group−1
For the ineffective dose of insulin aspart, and insulin resistant model is successfully established；The sugar absorption of α-mannatide individual processing
Rate is up to (1.8 ± 0.2) %；As α-mannatide and 0.1 nmol L−1When insulin aspart acts on jointly, cell membrane
The glucose absorption rate of type is 0.1nmol L−112 times of insulin aspart individual processing, 1nmol L−1Insulin aspart list
8 times and 10nmol L of reason of staying alone1 winter3 times of insulin individual processing, show that α-mannatide and insulin aspart exist
Promote that grape cell sugar has significant synergism on absorbing；As 10nmol L−1α-mannatide and 1000nmol
L−1When insulin aspart acts on jointly, the sugared absorbance of cell reaches maximum (35.3 ± 2.9) %.
Claims (6)
1. an insulin aspart injection, it is characterised in that in this injection containing insulin aspart, α-mannatide,
Zinc salt and antibacterial, the insulin aspart therein concentration in injection is 300-1200nmol/mL, and α-mannatide exists
Concentration in injection is 10-100nmol/mL.
Insulin aspart injection the most according to claim 1, it is characterised in that described insulin aspart is at injection
In concentration be 500-800nmol/mL, α-mannatide concentration in injection is 20-50nmol/mL.
Insulin aspart injection the most according to claim 1 and 2, it is characterised in that this injection uses pH adjusting agent
Tune pH value is 4.0-4.2.
Insulin aspart injection the most according to claim 3, it is characterised in that described insulin aspart is at injection
In concentration be 600nmol/mL, α-mannatide concentration in injection is 30nmol/mL, this injection use pH
Regulator adjusts pH value to be 4.2.
Insulin aspart injection the most according to claim 1 and 2, it is characterised in that described antibacterial is metacresol, institute
The zinc salt stated is zinc chloride.
6. the preparation method of an insulin aspart injection, it is characterised in that the method comprises the steps:
(1) α-mannatide is joined in the water for injection of 30-80% full dose and is stirred to dissolve, regulate pH to 4.0-4.2,
Add insulin aspart and stirring makes it dissolve, standby；
(2) zinc salt and antibacterial are joined in the water for injection of surplus, be stirred to dissolve, standby；
(3) solution that step (1) is prepared is joined in the solution that step (2) is prepared under agitation, mix homogeneously, regulation
Medicinal liquid pH value, to 4.0-4.2, filtration sterilization, fill, obtains insulin aspart injection.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610736379.1A CN106177917B (en) | 2016-08-29 | 2016-08-29 | A kind of insulin aspart injection and preparation method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610736379.1A CN106177917B (en) | 2016-08-29 | 2016-08-29 | A kind of insulin aspart injection and preparation method thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN106177917A true CN106177917A (en) | 2016-12-07 |
| CN106177917B CN106177917B (en) | 2019-11-19 |
Family
ID=57525965
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201610736379.1A Active CN106177917B (en) | 2016-08-29 | 2016-08-29 | A kind of insulin aspart injection and preparation method thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN106177917B (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113896784A (en) * | 2021-10-18 | 2022-01-07 | 合肥天麦生物科技发展有限公司 | Preparation method of insulin crystal and product thereof |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1429558A (en) * | 2003-01-24 | 2003-07-16 | 海南豪迈医药有限公司 | Mannosan peptide injection and its preparation and use method |
| CN102199206A (en) * | 2011-03-17 | 2011-09-28 | 甘李药业有限公司 | Insulin analogue having quick response and stability under acidic condition and preparation thereof |
| CN102580060A (en) * | 2011-01-08 | 2012-07-18 | 山东新时代药业有限公司 | Medicine composition for curing diabetes mellitus and complications of diabetes mellitus |
| CN103342746A (en) * | 2013-07-26 | 2013-10-09 | 珠海联邦制药股份有限公司 | Method for preparing stable insulin aspart crystal |
-
2016
- 2016-08-29 CN CN201610736379.1A patent/CN106177917B/en active Active
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1429558A (en) * | 2003-01-24 | 2003-07-16 | 海南豪迈医药有限公司 | Mannosan peptide injection and its preparation and use method |
| CN102580060A (en) * | 2011-01-08 | 2012-07-18 | 山东新时代药业有限公司 | Medicine composition for curing diabetes mellitus and complications of diabetes mellitus |
| CN102199206A (en) * | 2011-03-17 | 2011-09-28 | 甘李药业有限公司 | Insulin analogue having quick response and stability under acidic condition and preparation thereof |
| CN103342746A (en) * | 2013-07-26 | 2013-10-09 | 珠海联邦制药股份有限公司 | Method for preparing stable insulin aspart crystal |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113896784A (en) * | 2021-10-18 | 2022-01-07 | 合肥天麦生物科技发展有限公司 | Preparation method of insulin crystal and product thereof |
| CN113896784B (en) * | 2021-10-18 | 2024-04-16 | 合肥天麦生物科技发展有限公司 | Preparation method of insulin crystal and product thereof |
Also Published As
| Publication number | Publication date |
|---|---|
| CN106177917B (en) | 2019-11-19 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Lo et al. | Effects of ingested fruiting bodies, submerged culture biomass, and acidic polysaccharide glucuronoxylomannan of Tremella mesenterica Retz.: Fr. on glycemic responses in normal and diabetic rats | |
| CN110404161A (en) | A kind of transdermal accurate drug delivery device and preparation method thereof based on micropin formula ion nestocalyx part | |
| CN104257696A (en) | Yeast powder for reducing and stabilizing blood sugar as well as preparation method and application of yeast powder | |
| Song et al. | Selenium-loaded cellulose film derived from Styela clava tunic accelerates the healing process of cutaneous wounds in streptozotocin-induced diabetic Sprague–Dawley rats | |
| EP3574912B1 (en) | Composition for treating diabetic disease | |
| CN106177917A (en) | A kind of insulin aspart injection and preparation method thereof | |
| CN102335185A (en) | Purpose of icariin in preparation of medicines used for treating bronchial asthma | |
| CN109806256A (en) | Pinocembrin is in preparation for treating the application in pulmonary fibrosis disease drug | |
| CN104399059A (en) | Use of antimicrobial peptide AWRK6 in preparation of drug for treating type 2 diebetes | |
| CN101444480A (en) | Spirulina polysaccharide eye drop, and preparation method and application thereof | |
| CN109090512A (en) | A kind of hypoglycemic Thallus Laminariae (Thallus Eckloniae) extract | |
| TWI594749B (en) | Use of preparing lycogen composition for diabetic wound recovery and adjunctive treatment in cancer metastasis | |
| CN111388761B (en) | Application of gastrodin in medical titanium metal use in diabetes environment | |
| CN106466325B (en) | A kind of drug, composition and its preparation prevented or treat diabetes | |
| Dharma et al. | Effect of Fibroblast Growth Factor Combination with Ethanol Extract of Morinda citrifolia L. on Blood Glucose levels | |
| CN103845727B (en) | Nasal administration composition of recombination human ciliary neurotrophy factor and preparation method thereof | |
| US20230008796A1 (en) | Method of treating pancreas damage | |
| CN102349925A (en) | Application of astragaloside in preparation of drugs for promoting epithelization in wound healing | |
| RU2405559C2 (en) | Method of treating diabetes mellitus | |
| Jun et al. | Effects of Shuang Dan Ming Mu Capsule on expression of VEGF-a, VEGF-b, VEGF-c and the VEGF receptor, Flk-1, in diabetic retinopathy rats | |
| CN118021781A (en) | Application of small molecular compound in preparing medicament for treating or improving pituitary prolactin cell aging and promoting prolactin secretion | |
| Granda et al. | Sodium and potassium clearance rhythmicity in diabetic rats with insulin treatment | |
| CN108949669A (en) | It is a kind of for treating the preparation method and application of the cell combination preparation of type-1 diabetes mellitus | |
| UA140521U (en) | METHOD OF TREATMENT OF DIABETES MELLITUS | |
| CN109730991A (en) | Radix Zanthoxyli element is in preparation for treating the application in pulmonary fibrosis disease drug |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |