CN115400076A - Formula of recombinant human growth hormone-Fc fusion protein injection preparation - Google Patents
Formula of recombinant human growth hormone-Fc fusion protein injection preparation Download PDFInfo
- Publication number
- CN115400076A CN115400076A CN202210988804.1A CN202210988804A CN115400076A CN 115400076 A CN115400076 A CN 115400076A CN 202210988804 A CN202210988804 A CN 202210988804A CN 115400076 A CN115400076 A CN 115400076A
- Authority
- CN
- China
- Prior art keywords
- growth hormone
- recombinant human
- fusion protein
- human growth
- injection
- 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
Images
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
- A61K38/27—Growth hormone [GH] (Somatotropin)
-
- 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
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/16—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing nitrogen, e.g. nitro-, nitroso-, azo-compounds, nitriles, cyanates
- A61K47/18—Amines; Amides; Ureas; Quaternary ammonium compounds; Amino acids; Oligopeptides having up to five amino acids
- A61K47/183—Amino acids, e.g. glycine, EDTA or aspartame
-
- 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
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/22—Heterocyclic compounds, e.g. ascorbic acid, tocopherol or pyrrolidones
-
- 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
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/26—Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
-
- 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
- A61K47/50—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 the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/51—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 the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
- A61K47/68—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 the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P5/00—Drugs for disorders of the endocrine system
- A61P5/06—Drugs for disorders of the endocrine system of the anterior pituitary hormones, e.g. TSH, ACTH, FSH, LH, PRL, GH
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
Abstract
The invention discloses a formula of a recombinant human growth hormone-Fc fusion protein injection preparation, which belongs to the technical field of biological medicine and comprises 25-35mg/mL of the recombinant human growth hormone-Fc fusion protein, 1.24-1.86mg/mL of L-histidine, 30-60mg/mL of sucrose, 1880.5-3.0mg/mL of poloxamer, 5.0-30.0mg/mL of glycine and the balance of water for injection; the preparation process does not need a complex freeze-drying process, and the recombinant human growth hormone-Fc fusion protein has high stability in an injection preparation and is convenient to transport and store; the content and concentration of the recombinant human growth hormone-Fc fusion protein in the injection preparation are determined, concentration errors caused by re-dissolution are avoided, accurate administration is facilitated, compared with the traditional freeze-dried preparation, re-dissolution injection is not needed in buffering, the use is more convenient, the safety is higher, and the injection preparation has important clinical significance.
Description
Technical Field
The invention belongs to the technical field of biological medicines, and particularly relates to a formula of a recombinant human growth hormone-Fc fusion protein injection.
Background
Human growth hormone (hGH) is a peptide hormone which is a protein hormone synthesized, stored and secreted by growth hormone cells in the pituitary. The growth hormone molecule is composed of 191 amino acid residues, has a relative molecular mass of 22124 daltons, is combined with a receptor (hGHR) thereof on the surface of a target cell, activates biological reaction, and promotes the development of animals and human and the proliferation of the cell. Has the functions of regulating metabolism, stimulating protein synthesis, accelerating fat metabolism, promoting growth and development of bone and muscle tissues and the like, and is a specific medicine for treating short stature of children. The height problem of children is more and more concerned about, and the demand for improving the height is also more and more big. Causes of short stature in children are as many as 10, with Growth Hormone Deficiency (GHD) and idiopathic short stature being the most common. The recombinant human growth hormone (rhGH) is mainly used for treating or relieving childhood dwarfism, tissue repair, burns and scalds, adult Growth Hormone Deficiency (GHD) and the like caused by insufficient or deficient secretion of the Growth Hormone (GH). The recombinant human growth hormone-Fc fusion protein (rhGH-Fc) is produced by combining human growth hormone and an antibody Fc domain together through a connecting peptide to form a homodimer by using a gene recombination technology and utilizing Chinese Hamster Ovary (CHO). The amino acid content and sequence of the recombinant human growth hormone-Fc fusion protein (rhGH-Fc) N-terminal growth hormone are completely the same as those of human growth hormone, and the recombinant human growth hormone-Fc fusion protein has the same function as human endogenous growth hormone; the C terminal of the mutant is a human IgG subtype antibody Fc domain mutant, the half life of the medicine can be prolonged through a neonatal Fc receptor (FcRn) mediated recirculation mechanism, the injection is only needed once every week or every two weeks, the curative effect of the mutant is the same as that of recombinant human growth hormone (rhGH), the injection frequency is lower, and the medicine compliance and the overall therapeutic effect of a patient can be obviously improved. The rhGH-Fc does not need additional chemical modification, has lower potential safety hazard, high expression level, stable and reliable product preparation process and easy quality control.
The recombinant human growth hormone is an unstable macromolecular protein and is easy to generate changes such as oxidation, deamidation, polymerization and the like in aqueous solution. At present, the recombinant human growth hormone on the market is mostly prepared into powder injection by adopting a freeze drying technology, and the powder injection needs to be re-dissolved and injected by a patient, so that the use of the patient is complicated and the potential safety hazard of pollution exists. Therefore, the formula of the recombinant human growth hormone-Fc fusion protein injection is provided.
Disclosure of Invention
The invention aims to provide a formula of a recombinant human growth hormone-Fc fusion protein injection preparation so as to solve the problems in the background art.
The purpose of the invention can be realized by the following technical scheme:
the formula of the recombinant human growth hormone-Fc fusion protein injection comprises the following components:
25-35mg/mL of recombinant human growth hormone-Fc fusion protein, 1.24-1.86mg/mL of L-histidine, 30-60mg/mL of sucrose, 1880.5-3.0mg/mL of poloxamer, 5.0-30.0mg/mL of glycine and the balance of water for injection.
Further, the pH value of the recombinant human growth hormone-Fc fusion protein injection preparation is 6.0-8.0.
Furthermore, the L-histidine and the water for injection form an L-histidine buffer solution, and the L-histidine buffer solution is used as a basic buffer system of the recombinant human growth hormone-Fc fusion protein injection, so that the recombinant human growth hormone-Fc fusion protein is more stable.
Furthermore, glycine can improve the stability of the recombinant human growth hormone-Fc fusion protein injection under the illumination condition, and the preparation is more stable under the illumination condition when the concentration of the recombinant human growth hormone-Fc fusion protein is lower, the pH of an L-histidine buffer solution is higher, and the concentration of sucrose is higher in a certain range.
Furthermore, the recombinant human growth hormone-Fc fusion protein is 27-33mg/mL, L-histidine is 1.30-1.55mg/mL, sucrose is 40-50mg/mL, poloxamer 1880.8-1.2mg/mL, glycine is 9.6-14.4mg/mL, and the balance is water for injection.
Further, the pH value of the recombinant human growth hormone-Fc fusion protein injection preparation is 6.3-7.3.
The invention has the beneficial effects that:
the preparation formula of the recombinant human growth hormone-Fc fusion protein injection adopts an L-histidine buffer solution as a basic buffer solution, wherein L-histidine is a pH regulator; sucrose acts as a protein stabilizer and an isoosmotic adjusting agent; poloxamer 188 acts as a solubilizer and a surfactant; the glycine functions as an antioxidant and a pH regulator; the preparation process does not need a complex freeze-drying process, and the recombinant human growth hormone-Fc fusion protein has high stability in an injection preparation and is convenient to transport and store; the content and concentration of the recombinant human growth hormone-Fc fusion protein in the injection preparation are determined, concentration errors caused by re-dissolution are avoided, accurate administration is facilitated, compared with the traditional freeze-dried preparation, re-dissolution injection is not needed in buffering, the use is more convenient, the safety is higher, and the injection preparation has important clinical significance.
Drawings
The invention is further described below with reference to the accompanying drawings.
FIG. 1 is a line graph of SEC-HPLC purity (40-2W) of key influencing factors of DOE screening recombinant human growth hormone-Fc fusion protein injection formulation according to the present invention;
FIG. 2 is the SEC-HPLC purity (40 ℃ -2W) main effect graph of the key influencing factor of DOE screening recombinant human growth hormone-Fc fusion protein injection formulation of the present invention;
FIG. 3 is a line graph of SEC-HPLC purity (40-6W) of key influencing factors of DOE screening recombinant human growth hormone-Fc fusion protein injection formulation according to the present invention;
FIG. 4 is SEC-HPLC purity (40 ℃ -6W) main effect graph of DOE screening recombinant human growth hormone-Fc fusion protein injection formulation key influencing factor of the present invention;
FIG. 5 is a line graph of SEC-HPLC purity (25 ℃ -1M) and the like for DOE screening of key influencing factors of recombinant human growth hormone-Fc fusion protein injection formula;
FIG. 6 is the SEC-HPLC purity (25 ℃ -1M) main effect graph of the key influencing factor of DOE screening recombinant human growth hormone-Fc fusion protein injection formulation of the present invention;
FIG. 7 is a line graph of SEC-HPLC purity (25 ℃ -2M) and the like of the key influencing factors of DOE screening recombinant human growth hormone-Fc fusion protein injection formulation of the present invention;
FIG. 8 is the SEC-HPLC purity (25 ℃ -2M) main effect graph of the key influencing factor of DOE screening recombinant human growth hormone-Fc fusion protein injection formulation of the present invention;
FIG. 9 is a Pareto chart of SEC-HPLC purity (light-5D) normalization effect of DOE screening recombinant human growth hormone-Fc fusion protein injection formulation key influencing factor of the present invention;
FIG. 10 is a SEC-HPLC purity (light-5D) main effect chart of the key influencing factor of DOE screening recombinant human growth hormone-Fc fusion protein injection formulation.
Detailed Description
The technical solutions in the embodiments of the present invention will be clearly and completely described below with reference to the embodiments of the present invention, and it is obvious that the described embodiments are only a part of the embodiments of the present invention, and not all of the embodiments. All other embodiments, which can be derived by a person skilled in the art from the embodiments given herein without making any creative effort, shall fall within the protection scope of the present invention.
Example 1
The basic buffer solution for screening the recombinant human growth hormone-Fc fusion protein injection comprises the following steps:
step 1: selecting 8 common basic buffer solutions (please refer to table 1) for protein injection, defining the basic buffer solutions as 8 experimental groups, measuring 69.5mL (188.35 mg) of recombinant human growth hormone-Fc fusion protein qualified for detection respectively for each experimental group, placing the recombinant human growth hormone-Fc fusion protein into an ultrafiltration concentration tube for concentration, and obtaining 8 experimental group samples;
TABLE 1
Step 2: adding different basic buffer solutions into each experimental group sample in the step 1 for liquid change, wherein the liquid change volume is 9 +/-1 times of the volume; then preparing the concentration of each experimental group sample to 30 +/-5 mg/mL by using a corresponding buffer solution, filtering and subpackaging by using a 0.22 mu m microporous filter membrane under an aseptic environment to obtain subpackaged samples;
and step 3: the aliquots of the sample from step 2 were each tested for stability at a temperature of 40. + -. 2 ℃ with a humidity of 60. + -.5% RH and repeated freeze-thawing (-30. + -. 10 ℃ C., 12h, 25. + -. 2 ℃ C., 12h; 5 cycles). SEC-HPLC purity results and RP-HPLC purity results of recombinant human growth hormone-Fc fusion protein injection basic buffer screening were recorded and shown in tables 2 and 3, respectively (unit:%):
TABLE 2
TABLE 3
As can be seen from Table 2, the stability of the recombinant human growth hormone-Fc fusion protein in a histidine buffer system is significantly higher than that in a phosphate buffer system; as can be seen from Table 3, the recombinant human growth hormone-Fc fusion protein was most stable in the experimental group 6 (10 mM L-histidine buffer (pH 6.5)) under the conditions of 40. + -. 2 ℃ (60. + -.5% RH).
Example 2
The key influencing factor of the recombinant human growth hormone-Fc fusion protein injection is screened by a DOE experimental design method, and the method comprises the following steps:
step 1: taking an L-histidine buffer solution as a basic buffer solution of the recombinant human growth hormone-Fc fusion protein injection, selecting 5 factors (protein concentration, buffer system pH, mannitol concentration, sucrose concentration and Tween 80 concentration) to carry out five-factor and two-level DOE part experiment design (resolution is V), and performing 19 groups of experiments; buffer mother liquor required for the test was prepared as in table 4;
TABLE 4
And 2, step: using the buffer solution mother liquor in the step 1 and preparing a basic buffer solution required by an experiment according to the table 5;
TABLE 5
And step 3: using the buffer mother liquor in step 1 and preparing an auxiliary material concentrated solution (4 times concentrated) required by the experiment according to table 6;
TABLE 6
And 4, step 4: measuring qualified recombinant human growth hormone-Fc fusion protein by using the buffer solution in the step 2 according to the experimental requirements of the table 7, and performing concentrated solution replacement (TFF) operation;
TABLE 7
And 5: preparing a recombinant human growth hormone-Fc fusion protein injection preparation by using the buffer solution in the step 2, the auxiliary material concentrated solution in the step 3 and the concentrated solution change samples (TFF 1, TFF2, TFF3, TFF4 and TFF 5) in the step 4 according to the material proportion in the table 8, and filtering and subpackaging each experimental group sample by using a 0.22 mu m filter membrane under an aseptic environment after the preparation is finished; the formulation components corresponding to each experimental group are shown in table 9;
TABLE 8
TABLE 9
Step 6: the preparations of each experimental component in step 5 were individually subjected to 40. + -. 2 ℃ (60. + -.5 RH), 25. + -.2 ℃ (60. + -.5% RH), and illumination (illumination intensity 4500. + -.500lx, 5. + -.3 ℃, UV intensity 200 hw), and analyzed for SEC-HPLC purity as a response.
Referring to fig. 1 to 10, under accelerated experimental conditions, the protein concentration, the buffer pH and the sucrose concentration of the recombinant human growth hormone-Fc fusion protein injection have a significant effect on the degree of protein aggregation/degradation, and within a certain range, the lower the protein concentration, the higher the buffer pH and the higher the sucrose concentration, the more stable the sample. The recombinant human growth hormone-Fc fusion protein injection with low protein concentration is more stable under the condition of illumination.
Example 3
The formula of the recombinant human growth hormone-Fc fusion protein injection optimized by a univariate experimental method comprises the following steps:
step 1: according to the experimental results of example 1 and example 2, 8 experiments in this experiment all used L-histidine buffer as the basic buffer, the concentration of recombinant human growth hormone-Fc fusion protein was 30mg/mL, and the concentration of sucrose was 50mg/mL, on the basis of which the influence of tween 80, poloxamer 188 and glycine on the stability of the recombinant human growth hormone-Fc fusion protein injection solution was investigated by changing the concentration of tween 80, the concentration of poloxamer 188 and the concentration of glycine.
The solutions required for the univariate experiments were prepared as per table 10:
watch 10
And 2, step: preparing an auxiliary material concentrated solution required by a univariate experiment by using the solution in the step 1 according to the material ratio in the table 11;
TABLE 11
And step 3: using the solution in the step 1 and the adjuvant concentrated solution in the step 2, respectively measuring 156mg of qualified recombinant human growth hormone-Fc fusion protein stock solution for each experimental component, preparing a recombinant human growth hormone-Fc fusion protein injection preparation according to the material ratio in the table 12, filtering each experimental component sample with a 0.22 μm filter membrane in a sterile environment, and subpackaging; the formulation components corresponding to each experimental group are shown in table 13;
TABLE 12
Watch 13
And 4, step 4: the preparations obtained by dividing each experimental component in step 3 were subjected to repeated freeze-thawing at 40. + -. 2 ℃ (60. + -.5% RH), 25. + -.2 ℃ (60. + -.5% RH), 5. + -.3 ℃ (12 h at 30. + -.10 ℃,12h at 25. + -.2 ℃ after removal, 5 cycles), light (4500. + -.500lx, 5. + -.3 ℃ C., UV 200hw intensity), shaking (180rpm, 5. + -.3 ℃ C.), etc., to test the SEC-HPLC purity and RP-HPLC purity, and the results are shown in tables 14 and 15.
TABLE 14
As can be seen from Table 14, the SEC-HPLC purities were not significantly degraded in all experimental groups in example 3 under the conditions of 25. + -. 2 ℃ (60. + -.5% RH) -3M, 5. + -.3 ℃ -6M, repeated freeze-thaw-5T (5 times), and shaking-5D (180rpm, 5. + -.3 ℃); the SEC-HPLC purity result under the condition of illumination-10D (illumination intensity of 4500 +/-500lx, 5 +/-3 ℃ and ultraviolet intensity of 200 hw) shows that glycine can improve the stability of a sample under the illumination condition, and the glycine content in the preparation is 12mg/mL and 25mg/mL, and has no obvious difference on the stability of the recombinant human growth hormone-Fc fusion protein under the illumination condition.
Watch 15
As can be seen from Table 15, in example 3, all experimental groups showed no significant decrease in RP-HPLC purity under the conditions of 5 + -3 deg.C-6M, repeated freeze-thaw-5T, and shaking-5D (180rpm, 5 + -3 deg.C).
According to the experimental result, the formula of the recombinant human growth hormone-Fc fusion protein injection is determined as follows:
25-35mg/mL of recombinant human growth hormone-Fc fusion protein, 1.24-1.86mg/mL of L-histidine, 30-60mg/mL of sucrose, 1880.5-3.0mg/mL of poloxamer, 5.0-30.0mg/mL of glycine and the balance of water for injection.
It should be noted that, in this document, terms such as "comprises," "comprising," or any other variation thereof, are intended to cover a non-exclusive inclusion, such that a process, method, article, or apparatus that comprises a list of elements does not include only those elements but may include other elements not expressly listed or inherent to such process, method, article, or apparatus.
Although embodiments of the present invention have been shown and described, it will be appreciated by those skilled in the art that changes, modifications, substitutions and alterations can be made in these embodiments without departing from the principles and spirit of the invention, the scope of which is defined in the appended claims and their equivalents.
Claims (4)
1. The formula of the recombinant human growth hormone-Fc fusion protein injection is characterized by comprising the following components:
25-35mg/mL of recombinant human growth hormone-Fc fusion protein, 1.24-1.86mg/mL of L-histidine, 30-60mg/mL of sucrose, 1880.5-3.0mg/mL of poloxamer, 5.0-30.0mg/mL of glycine and the balance of water for injection.
2. The formulation of the recombinant human growth hormone-Fc fusion protein injection formulation of claim 1, wherein the pH of the recombinant human growth hormone-Fc fusion protein injection formulation is between 6.0 and 8.0.
3. The formulation of recombinant human growth hormone-Fc fusion protein injection according to claim 1, comprising the following components:
27-33mg/mL of recombinant human growth hormone-Fc fusion protein, 1.30-1.55mg/mL of L-histidine, 40-50mg/mL of sucrose, 1880.8-1.2mg/mL of poloxamer, 9.6-14.4mg/mL of glycine and the balance of water for injection.
4. The formulation of claim 3, wherein the recombinant human growth hormone-Fc fusion protein injection has a pH of 6.3-7.3.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202210988804.1A CN115400076B (en) | 2022-08-17 | 2022-08-17 | Recombinant human growth hormone-Fc fusion protein injection formulation |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202210988804.1A CN115400076B (en) | 2022-08-17 | 2022-08-17 | Recombinant human growth hormone-Fc fusion protein injection formulation |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN115400076A true CN115400076A (en) | 2022-11-29 |
| CN115400076B CN115400076B (en) | 2023-09-05 |
Family
ID=84158672
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202210988804.1A Active CN115400076B (en) | 2022-08-17 | 2022-08-17 | Recombinant human growth hormone-Fc fusion protein injection formulation |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN115400076B (en) |
Citations (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1665541A (en) * | 2002-07-09 | 2005-09-07 | 桑多斯股份公司 | Liquid formulations with a high concentration of human growth hormone (hgh) comprising glycine |
| CN102302446A (en) * | 2011-09-08 | 2012-01-04 | 安徽安科生物工程（集团）股份有限公司 | Recombinant human growth hormone injection capable of being directly used |
| CN108404121A (en) * | 2018-05-28 | 2018-08-17 | 中山未名海济生物医药有限公司 | A kind of recombinant human growth hormone injection and preparation method thereof |
| CN110256575A (en) * | 2019-06-11 | 2019-09-20 | 长春生物制品研究所有限责任公司 | A kind of long-acting recombinant human growth hormone fusion protein and its engineering cell |
| CN111329996A (en) * | 2020-03-03 | 2020-06-26 | 上海联合赛尔生物工程有限公司 | Composition of recombinant human growth hormone and preparation method thereof |
| CN112494638A (en) * | 2020-12-22 | 2021-03-16 | 深圳科兴药业有限公司 | Human growth hormone injection composition and preparation method thereof |
| CN112661858A (en) * | 2020-12-03 | 2021-04-16 | 安徽安科生物工程（集团）股份有限公司 | Recombinant human growth hormone Fc fusion protein, application and engineering cell strain thereof |
| US20210188941A1 (en) * | 2018-05-25 | 2021-06-24 | Dr. Reddy's Laboratories Limited | Stable fusion protein formulation |
-
2022
- 2022-08-17 CN CN202210988804.1A patent/CN115400076B/en active Active
Patent Citations (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1665541A (en) * | 2002-07-09 | 2005-09-07 | 桑多斯股份公司 | Liquid formulations with a high concentration of human growth hormone (hgh) comprising glycine |
| CN102302446A (en) * | 2011-09-08 | 2012-01-04 | 安徽安科生物工程（集团）股份有限公司 | Recombinant human growth hormone injection capable of being directly used |
| US20210188941A1 (en) * | 2018-05-25 | 2021-06-24 | Dr. Reddy's Laboratories Limited | Stable fusion protein formulation |
| CN108404121A (en) * | 2018-05-28 | 2018-08-17 | 中山未名海济生物医药有限公司 | A kind of recombinant human growth hormone injection and preparation method thereof |
| CN110256575A (en) * | 2019-06-11 | 2019-09-20 | 长春生物制品研究所有限责任公司 | A kind of long-acting recombinant human growth hormone fusion protein and its engineering cell |
| CN111329996A (en) * | 2020-03-03 | 2020-06-26 | 上海联合赛尔生物工程有限公司 | Composition of recombinant human growth hormone and preparation method thereof |
| CN112661858A (en) * | 2020-12-03 | 2021-04-16 | 安徽安科生物工程（集团）股份有限公司 | Recombinant human growth hormone Fc fusion protein, application and engineering cell strain thereof |
| CN112494638A (en) * | 2020-12-22 | 2021-03-16 | 深圳科兴药业有限公司 | Human growth hormone injection composition and preparation method thereof |
Non-Patent Citations (1)
| Title |
|---|
| 王健 等: "液体生长激素注射液的应用现状", 中国药师 * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN115400076B (en) | 2023-09-05 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CA2102693C (en) | Protein formulation comprising growth hormone | |
| JP6143827B2 (en) | Formulation for combination of hGH and rhIGF-1 | |
| CN1198644C (en) | Stabilized teriparatide solutions | |
| CA1267995A (en) | Biologically active peptides structurally related to regions within growth hormones | |
| CN105121459A (en) | Method of increasing the hydrodynamic volume of polypeptides by attaching to gonadotrophin carboxy terminal peptides | |
| CN109851674B (en) | Preparation and purification method of recombinant human serum albumin/growth hormone fusion protein for treating children's dwarf syndrome | |
| CN108883061B (en) | Stable liquid gonadotropin formulations | |
| US20060147480A1 (en) | Liquid pharmaceutical formulations of fsh and lh together with a non-ionic surfactant | |
| MOORE et al. | Equivalent potency and pharmacokinetics of recombinant human growth hormones with or without an N-terminal methionine | |
| PT1951395E (en) | Method for the quantitative determination of poloxamers | |
| JPH08505617A (en) | Stable solution containing insulin-like growth factor | |
| EP1034007B1 (en) | METHOD FOR THE PRODUCTION OF A ONE DOSE SYRINGE, COMPRISING A FREEZE-DRIED PROTEIN COMPOSITION, FOR ADMINISTERING A VOLUME LESS THAN 0.5 ml | |
| CN115400076A (en) | Formula of recombinant human growth hormone-Fc fusion protein injection preparation | |
| JP4949828B2 (en) | Stabilization of growth hormone in solution | |
| AU2013368990B2 (en) | Pharmaceutical composition | |
| KR20090118879A (en) | Human growth hormone derivative linked with polyethyleneglycol, method for the preparation thereof and pharmaceutical composition comprising the same | |
| JP2000178203A (en) | Use of human growth hormone for stimulating hematopoiesis and immune restoration after hematopoietic stem cell implanting in human | |
| Miyabo et al. | Stimulation of the hypothalamic-pituitary-adrenal axis by epidermal growth factor | |
| Jørgensen et al. | Development, production and pharmacodynamics of human growth hormone | |
| KR20120139299A (en) | Stable lyophilized composition for injection comprising epidermal growth factor |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |