CN106309358A - Human parathyroid hormone-containing pharmaceutical composition and preparing method and use thereof - Google Patents
Human parathyroid hormone-containing pharmaceutical composition and preparing method and use thereof Download PDFInfo
- Publication number
- CN106309358A CN106309358A CN201510367315.4A CN201510367315A CN106309358A CN 106309358 A CN106309358 A CN 106309358A CN 201510367315 A CN201510367315 A CN 201510367315A CN 106309358 A CN106309358 A CN 106309358A
- Authority
- CN
- China
- Prior art keywords
- pharmaceutical composition
- rhpth
- concentration
- stabilizer
- lyophilized formulations
- 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.)
- Pending
Links
Abstract
The invention relates to a human parathyroid hormone rhPTH(1-34)-containing pharmaceutical composition; a composition of sucrose and mannitol is used as a stabilizer, the pharmaceutical composition has the characteristics of simple components, good stability and the like, and a freeze-dried preparation further prepared from the pharmaceutical composition has the characteristics of high stability, good resolubility and the like, and meets the requirements of clinical medication. The invention also provides a preparing method of the pharmaceutical composition, a method for preparing the freeze-dried preparation, and a use of the pharmaceutical composition in preparation of medicines for treating and/or preventing osteoporosis.
Description
Technical field
The present invention relates to field of medicaments, more specifically, the present invention relates to a kind of pharmaceutical composition containing human thyroid stimulator and preparation method thereof, and this pharmaceutical composition is for preparing the method for lyophilized formulations and the purposes in terms for the treatment of and/or pre-anti-osteoporosis thereof.
Background technology
Osteoporosis is a kind of low with bone amount, and bone micro-structure breaks ring and causes bone fragility to increase, and the common systemic disease that fracture is characterized easily occurs, and mid-aged population in serious threat, and especially postmenopausal women is healthy.At present, the whole world there are about more than 200,000,000 crowds and suffers from osteoporosis, its sickness rate leapt to commonly encountered diseases, the 6th of frequently-occurring disease.It is the first that China's sufferers of osteoporosis face occupy the world, about 90,000,000 people, is about 15.7% in its incidence rate crowd more than 50 years old, in crowd more than 60 years old about 56%, wherein postmenopausal women's incidence rate is higher than male, is 60～70%, typically occurs in 5～10 years after postmenopausal women.Along with the development of social senilization, the sickness rate of osteoporosis is in rising trend, it is contemplated that will be added to 2.21 hundred million to the year two thousand fifty.
At present, for treating the drug main of postmenopausal osteoporosis estrogen to be had, selective estrogen receptor modulators, Diphosphonate and calcium element etc., these drug mains to improve bone density by suppression bone resorption, but can not maintain normal bone amount and bone strength, and the medicine of promoting bone growing can compensate its defect.
Parathyroid hormone (Parathyroid Hormone, PTH) it is a kind of single chain polypeptide hormone being synthesized by chief cell and secreting, ripe PTH contains 84 amino acid residues, being one of regulation alcium and phosphor metabolization and bone of paramount importance hormone of conversion in human body, low dose of intermittent administration can improve bone density, improve bone mass, the incidence rate of reduction fracture.Research shows, PTH biologic activity is essentially from its N end, as N end fragment PTH (1-34) remains the biologic activity of the complete peptide fragment of PTH, can promote that osteogenesis effectively treats osteoporosis, clinical practice use PTH (1-34) treat bone loss disorders more.
Ser Val Ser Glu Ile Gln Leu Met His Asn Leu Gly Lys His Leu Asn Ser Met Glu Arg
1 5 10 15 20
Val Glu Trp Leu Arg Lys Lys Leu Gln Asp Val Hi s Asn Phe
25 30
PTH (1-34) aminoacid sequence
The N-terminal of PTH (1-34) and the whether complete of C-terminal sequence determine its biological activity, and as a kind of macro-molecular protein, PTH (1-34) is particularly sensitive to oxidation, demidizate and hydrolysis so that ensure one of its N-terminal and the C-terminal sequence completely key problem in technology being to ensure that product quality in production, preparation and storage and transport process.
PTH (1-34) raw material many employings genetic engineering recombinant technique obtains at present, commercially available people recombinates PTH (rhPTH (1-34)) injection (Teriparatide, teriparatide) use prepackage type pen-type injector, its complex manufacturing, production cost is high, there is inconvenience in accumulating so that valuable product, its prescription mainly comprises glacial acetic acid, anhydrous sodium acetate, mannitol, metacresol and water for injection etc..Wherein, metacresol easily aoxidizes generation quinones and the compound of other complexity so that teriparatide injection is easily generated impurity during preparation and storage, causes injection products unstable, and life-time service metacresol is easily generated toxic and side effects to human body.
Therefore, finding rhPTH (1-34) formulation products that a kind of accumulating is convenient, easy to use, technique is simple, stability is high is that prior art does not solve the technical problem that.
Summary of the invention
The present invention is from solving the deficiencies in the prior art, provide a kind of stabilizing pharmaceutical composition containing rhPTH (1-34) and the lyophilized formulations obtained further thereof, this pharmaceutical composition can be used for large-scale production and prepares rhPTH (1-34) lyophilized formulations, and the lyophilized formulations prepared has the features such as stability is high, solubility is good.
The above-mentioned purpose of the present invention is achieved through the following technical solutions:
A kind of pharmaceutical composition containing rhPTH, described pharmaceutical composition is solution system, and its pH value is 6～7, and described pharmaceutical composition includes treating the rhPTH of effective dose, stabilizer, sodium chloride and pharmaceutically acceptable buffer agent.
Described rhPTH refers to rhPTH (1-34), can be prepared by existing known genetic engineering recombinant technique.In described pharmaceutical composition, rhPTH concentration is 50～60 μ g/ml, it is preferred that in described pharmaceutical composition, rhPTH concentration is 56.5 μ g/ml.
Described stabilizer is the compositions of sucrose and mannitol.Owing to N-terminal and the C-terminal of rhPTH (1～34) are unstable, on the one hand stabilizer can ensure that rhPTH (1-34) will not occur degradation reaction during preparation and storage, on the other hand can also play a supporting role in freeze-drying process.Concrete, one of main component as final products, selection to stabilizer needs to consider its Stabilization, supplementary material compatibility and the adaptability etc. for lyophilizing technique simultaneously, stabilizer of the present invention has polyhydroxy-sugar structure, and hydrophilic is strong, glassy state temperature is higher, can effectively stop the change of rhPTH (1-34) secondary structure, and make it remain to keep its biological activity after lyophilization is dried out；Additionally, stabilizer of the present invention the most also has effect expanded, that support in lyophilization, be conducive to being formed porosity and looseness powder when lyophilizing, it is simple to the removal of moisture in lyophilizing technique, it is ensured that the reconstruction of stability of rhPTH (1-34) lyophilized formulations.In described pharmaceutical composition there is selection in the concentration (consumption) of stabilizer, and rhPTH (1-34) protective effect will not be improved by excessive concentrations, and the protective effect in some formula can decline on the contrary；Cross low concentration to be not enough to form monolayer at rhPTH (1-34) protein surface; and can not effectively protect the activity of rhPTH (1-34); concrete; in described pharmaceutical composition, the concentration of stabilizer is 20～50mg/ml; more specifically; described stabilizer sucrose and the combination of mannitol, wherein sucrose concentration is 10～20mg/ml；Mannitol concentration is 10～30mg/ml, preferably 20mg/ml.
Described pharmaceutically acceptable buffer agent is disodium hydrogen phosphate/sodium dihydrogen phosphate, it is preferred that the buffer agent in described pharmaceutical composition is the combination of concentration 0.20～0.45mg/ml disodium hydrogen phosphate and concentration 0.25～1.20mg/ml sodium dihydrogen phosphate.The purpose selecting buffer agent is by pharmaceutical composition pH stable between 6～7, while ensureing stable effective ingredients, is ensured by the solubility of preparation in preferable state, and administration pain is reduced to minimum.
Described sodium chloride (NaCl) is osmotic pressure regulator, and its concentration in pharmaceutical composition is 0.50～1mg/ml.
The prescription Central Plains of above-mentioned rhPTH (1-34) pharmaceutical composition, adjuvant have preferable compatibility, the supplementary product kind comprised and consumption make prescription ensure that the stability of product on the whole, and most beneficial for follow-up production technology, and prepared the lyophilized formulations product meeting Clinical practice by subsequent technique.Obtained freeze-drying preparation has the characteristic of good stability equally, and has and preferably redissolve performance.
Another object of the present invention is to provide the preparation method of a kind of aforementioned Pharmaceutical composition containing rhPTH (1-34), and comprise the method that pharmaceutical composition is prepared as lyophilized formulations further, described method comprises the steps:
1) rhPTH (1-34) albumen stock solution is joined in the mixed solution containing stabilizer, NaCl and pharmaceutically acceptable buffer agent, mixing；
2) hydrochloric acid or sodium hydroxide solution is used to regulate system pH to 6～7；
3) degerming, aseptic subpackaged；
4) lyophilization, obtains described lyophilized formulations.
Described step 3) degerming preferred filtration sterilization；Described step 4) in
Cryodesiccated process farther includes:
A) pre-freeze；
B) primary drying；
C) redrying.
Pre-freezing temperature in described step a) is: room temperature～-45 DEG C, and the pre-freeze time is 2～4h；In described step b), primary drying temperature is :-40 DEG C～-20 DEG C, and the primary drying time is 10～15h, and vacuum is: 15～10Pa；In described step c), redrying temperature is :-15 DEG C～30 DEG C, and the redrying time is 10～15h, and vacuum is 10～2Pa.The temperature of described primary drying and redrying may select constant temperature, it is also possible to selects gradient alternating temperature to be dried.
One preferred freezing dry process of the present invention: use progressively falling temperature method, concrete, described pre-freezing temperature is room temperature～-45 DEG C, and the pre-freeze time is 3h；Described primary drying temperature is :-40 DEG C～-20 DEG C, and the primary drying time is 13h, and vacuum is: 15～10Pa；Described redrying temperature is :-15 DEG C～30 DEG C, and the redrying time is 11h, and vacuum is 10～2Pa.What described primary drying and redrying selected is that gradient alternating temperature is dried.
Third object of the present invention is to provide one containing rhPTH (1-34) Pharmaceutical composition in the purposes prepared in the medicine for the treatment of and/or pre-anti-osteoporosis.Owing to this pharmaceutical composition contains the rhPTH (1-34) of high concentration; effectively can must reduce clinical administration number of times/frequency; and use genetic engineering recombinant technique large-scale production rhPTH (1-34), the demand of clinical a large amount of medication can be met, there is good potential applicability in clinical practice.
The present invention has such advantages as relative to prior art and beneficial effect:
1, a kind of Pharmaceutical composition containing rhPTH (1-34) is provided, the features such as it is simple that described pharmaceutical composition has composition, good stability, its lyophilized formulations prepared further has the feature that stability is high equally, and its solubility is good, meet clinical application requirement；
2, the method that one prepares the pharmaceutical composition containing rhPTH (1-34) is provided, and gained pharmaceutical composition is further used for preparing the method for medicament freeze-drying preparation, this production method is conducive to preparing the lyophilized formulations product meeting clinical application requirement, and production method is simple, it is adaptable to industrialization large-scale production；
3, a kind of Pharmaceutical composition containing rhPTH (1-34) is provided in preparation for the application treated and/or in the medicine of pre-anti-osteoporosis, owing to this pharmaceutical composition contains the rhPTH (1-34) of high concentration, clinical administration number of times/frequency effectively can must be reduced；And composite formula safety non-toxic used, free from foreign meter, reduce the probability of medicine generation toxicity, effectively increase the compliance of rhPTH (1-34) medicine.
Detailed description of the invention
Below in conjunction with embodiment, the present invention is described in further detail, but the embodiment of invention is not limited to this.
The employing document of the protein stock solution containing rhPTH (1-34) that embodiment uses: Sung WL.J Biol Chem.1991；Prepared by the method for 266 (5): 2831-5..It is 2mg/ml that gained protein stock solution contains rhPTH (1-34) concentration, purity 98.0%.
Embodiment 1
Containing rhPTH (1-34) pharmaceutical composition and the preparation of lyophilized formulations thereof
1, containing the preparation of rhPTH (1-34) pharmaceutical composition
RhPTH (1-34) the albumen stock solution (purity 98%, concentration 2mg/ml) being prepared by recombinant is thawed at room temperature or 2～8 DEG C, in 2～8 DEG C of preservations after defrosting.According to each ratio of adjuvant of A-D in following table, precise stabilizer, sodium chloride, buffer agent respectively, it is formulated as mixed liquor after dissolving with 800mL water for injection, add rhPTH (1-34) the albumen stock solution after thawing, stirring and evenly mixing, hydrochloric acid or sodium hydroxide solution regulate to purpose pH value, and continuation water for injection is settled to 1L, be that 0.22 μm membrane filtration is degerming with aperture under aseptic condition, and aseptic subpackaged after respectively obtain A-D pharmaceutical composition.
0.20～0.45mg/ml disodium hydrogen phosphate and the combination of concentration 0.25～1.20mg/ml sodium dihydrogen phosphate
| Component | A | B | C | D |
| rhPTH(1-34)(μg/ml) | 56.5 | 56.5 | 50 | 60 |
| Disodium hydrogen phosphate (mg/ml) | 0.21 | 0.433 | 0.21 | 0.21 |
| Sodium dihydrogen phosphate (mg/ml) | 1.18 | 0.269 | 1.18 | 1.18 |
| Sucrose (mg/ml) | 11.2 | 20 | 11.2 | 11.2 |
| Mannitol (mg/ml) | 20 | 20 | 20 | 20 |
| NaCl(mg/ml) | 0.56 | 1 | 0.56 | 0.56 |
| pH | 6.0 | 7.0 | 6.0 | 6.0 |
| Loading amount (ml/ props up) | 1 | 1 | 1 | 1 |
2, containing the preparation of rhPTH (1-34) pharmaceutical composition lyophilized formulations
Pharmaceutical composition abovementioned steps prepared, prepares according to the lyophilizing technique of following table and is respectively lyophilized formulations A-D, specifically comprise the following steps that
(1) in the pre-freeze stage: temperature from ambient is down to-45 DEG C, then pharmaceutical composition is placed in-45 DEG C, maintaining 3h, vacuum is 0Pa.
(2) in the primary drying stage: maintaining vacuum is 15～10Pa, 1h at pharmaceutical composition is placed in-40 DEG C, it is dried；1h it is dried at-35 DEG C；1h it is dried at-30 DEG C；1h it is dried at-25 DEG C；9h it is dried at-20 DEG C；
(3) in the redrying stage: maintaining vacuum is 10～2Pa, 1h at pharmaceutical composition is placed in-15 DEG C, it is dried；1h it is dried at-10 DEG C；1h it is dried at-5 DEG C；3h it is dried at 0 DEG C；1h it is dried at 5 DEG C；1h it is dried at 10 DEG C；1h it is dried at 15 DEG C；1h it is dried at 20 DEG C；Being dried 1h at 30 DEG C, correspondence obtains lyophilized formulations A-D respectively.
All there is not to spray bottle phenomenon, and the white loosening body of freeze-dried powder in obtained freeze-drying preparation A-D, formability is good, and moisture removal fully, completely, meets clinical application quality control requirement.
Comparative example 1
Containing rhPTH (1-34) Pharmaceutical composition E and the preparation of lyophilized formulations thereof
1, containing the preparation of rhPTH (1-34) Pharmaceutical composition
RhPTH (1-34) the albumen stock solution (purity 98%, concentration 2mg/ml) that will be prepared by recombinant, in 2～8 DEG C of preservations after defrosting.According to each ratio of adjuvant of E in following table, precise stabilizer, sodium chloride, buffer agent respectively, it is formulated as mixed liquor after dissolving with 800mL water for injection, add rhPTH (1-34) the albumen stock solution after thawing, stirring and evenly mixing, regulating pH with hydrochloric acid or sodium hydroxide solution is 7.0, and continuation water for injection is settled to 1L, it is that 0.22 μm membrane filtration is degerming with aperture under aseptic condition, and aseptic subpackaged obtains E pharmaceutical composition.
| Component | E |
| rhPTH(1-34)(μg/ml) | 56.5 |
| Disodium hydrogen phosphate (mg/ml) | 0.433 |
| Sodium dihydrogen phosphate (mg/ml) | 0.269 |
| Mannitol (mg/ml) | 50 |
| NaCl(mg/ml) | 1 |
| PH value | 7.0 |
| Loading amount (ml/ props up) | 1 |
2, containing the preparation of rhPTH (1-34) Pharmaceutical composition lyophilized formulations
Step of freeze drying same as in Example 1 is used to prepare lyophilized formulations E.
There is not to spray bottle phenomenon, and the white loosening body of freeze-dried powder in obtained freeze-drying preparation E, formability is good, and moisture removal is fully, completely.
Comparative example 2
Containing rhPTH (1-34) Pharmaceutical composition F and the preparation of lyophilized formulations thereof
1, containing the preparation of rhPTH (1-34) Pharmaceutical composition
According to each ratio of adjuvant of F in following table, method same as in Example 1 is used to prepare F pharmaceutical composition.
| Component | F |
| rhPTH(1-34)(μg/ml) | 56.5 |
| Acetic acid (mg/ml) | 0.03 |
| Sodium acetate (mg/ml) | 1.6 |
| Sucrose (mg/ml) | 11.2 |
| NaCl(mg/ml) | 0.56 |
| PH value | 6.0 |
| Loading amount (ml/ props up) | 1 |
2, containing the preparation of rhPTH (1-34) Pharmaceutical composition lyophilized formulations
Step of freeze drying same as in Example 1 is used to prepare lyophilized formulations F.
Owing to pharmaceutical composition F uses very few stabilizer so that it is powder generation avalanche when preparing lyophilized formulations F so that lyophilized formulations F is shapeless, does not meets the requirement of clinical application quality control.
Embodiment 2
Solubility detects
Lyophilized formulations A-E is placed at 37 DEG C preservation, and use the method at " Chinese Pharmacopoeia " (2010) version appendix 26, described lyophilized formulations is dissolved respectively with 1.1ml water for injection, detect the situation of change of its time being completely dissolved in accelerating storage experimentation (redissolving the time), and observe outward appearance and the visible foreign matters of solution after dissolving, acquired results such as following table:
Understanding, lyophilized formulations A and B redissolves in 37 DEG C of Acceleration study and all meets clinical application prescription in terms of time, solution appearance and visible foreign matters, and all fluctuates without obvious.Repeating it was found that, lyophilized formulations C and D also can reach the clinical application prescription as lyophilized formulations A and B.
For lyophilized formulations E; owing to not using claimed stabilizer; although making preparation be presented as achromaticity and clarification and foreign at 0 day; but find tiny albumen floccule in accelerated test after 1 week; and gradually it is polymerized to protein body with the carrying out of accelerated test, do not meet the relevant regulations of " Chinese Pharmacopoeia " (version in 2010).
Embodiment 3
Detection of Stability
Lyophilized formulations A and B is placed at 37 DEG C preservation, be respectively adopted cAMP algoscopy, RP-HPLC method detects lyophilized formulations A and B biologic activity, rhPTH (1-34) purity and change of peptide content in accelerating storage experimentation respectively, acquired results such as following table:
Test result indicate that, lyophilized formulations A and B rhPTH (1-34) purity when 0 day is more than 98%, and biologic activity also maintains higher level, it is known that the impact of lyophilizing technique characteristic every on rhPTH is less.
During storage subsequently, biological activity, rhPTH (1-34) purity and content fluctuation are less, and all maintain of a relatively high stability, meet clinical application prescription.
Lyophilized formulations C and D carries out under similarity condition stability experiment, and lyophilized formulations C and D can reach the stability experiment result basically identical with lyophilized formulations A and B.
In summary, and rhPTH (1-34) lyophilized formulations prepared by the present invention has good stability, biologic activity and solubility, and obtained freeze-drying preparation meets clinical application prescription.
Above-described embodiment is the present invention preferably embodiment; but embodiments of the present invention are also not restricted to the described embodiments; the change made under other any spirit without departing from the present invention and principle, modify, substitute, combine, simplify; all should be the substitute mode of equivalence, within being included in protection scope of the present invention.
Claims (12)
1. the pharmaceutical composition containing rhPTH (1-34), described pharmaceutical composition is solution system, its pH
Value is 6～7, and described pharmaceutical composition includes treating the rhPTH (1-34) of effective dose, stabilizer, chlorination
Sodium and pharmaceutically acceptable buffer agent, it is characterised in that described stabilizer is the compositions of sucrose and mannitol, described
The concentration of stabilizer is 20～50mg/ml.
Pharmaceutical composition the most according to claim 1, it is characterised in that in described stabilizer, sucrose concentration is
10-20mg/ml, mannitol concentration is 10-30mg/ml.
Pharmaceutical composition the most according to claim 2, it is characterised in that mannitol concentration in described stabilizer
For 20mg/ml.
4. according to the pharmaceutical composition described in claim 1-3 any one, it is characterised in that the effective agent of described treatment
RhPTH (1-34) concentration of amount is 50～60 μ g/ml.
5. according to the pharmaceutical composition described in claim 1-4 any one, it is characterised in that the effective agent of described treatment
RhPTH (1-34) concentration of amount is 56.5 μ g/ml.
6. according to the pharmaceutical composition described in claim 1-5 any one, it is characterised in that described pharmaceutically acceptable buffering
Agent is disodium hydrogen phosphate/sodium dihydrogen phosphate.
7. according to the pharmaceutical composition described in claim 1-6 any one, it is characterised in that described pharmaceutically acceptable buffering
Agent is 0.20～0.45mg/ml disodium hydrogen phosphate and the combination of 0.25～1.20mg/ml sodium dihydrogen phosphate.
8. according to the pharmaceutical composition described in claim 1-7 any one, it is characterised in that described sodium chloride is at medicine
Concentration in compositions is 0.50～1mg/ml.
9. it is used in preparation according to the Pharmaceutical composition of the rhPTH (1-34) described in claim 1-8 any one
Purposes in the medicine for the treatment of and/or pre-anti-osteoporosis.
10. the lyophilized formulations containing rhPTH (1-34), by the rhPTH described in claim 1-8 any one
(1-34) Pharmaceutical composition prepares.
The preparation method of the lyophilized formulations of 11. 1 kinds of rhPTH as claimed in claim 10 (1-34), its feature exists
Comprise the steps: in described preparation method
1) rhPTH (1-34) albumen stock solution is joined containing stabilizer, NaCl and the mixing of pharmaceutically acceptable buffer agent
In solution, mixing；
2) hydrochloric acid or sodium hydroxide solution is used to regulate system pH to 6～7；
3) degerming, aseptic subpackaged；
4) lyophilization, obtains described lyophilized formulations.
The preparation method of the lyophilized formulations of 12. 1 kinds of rhPTH as claimed in claim 11 (1-34), its feature exists
In described step 3) degerming for filtration sterilization；Described step 4) in cryodesiccated process farther include:
A) pre-freeze；
B) primary drying；
C) redrying.
Pre-freezing temperature in described step a) is: room temperature～-45 DEG C, and the pre-freeze time is 2～4h；In described step b) one
Secondary baking temperature is :-40 DEG C～-20 DEG C, and the primary drying time is 10～15h, and vacuum is: 15～10Pa；
In described step c), redrying temperature is :-15 DEG C～30 DEG C, and the redrying time is 10～15h, vacuum
It is 10～2Pa.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510367315.4A CN106309358A (en) | 2015-06-29 | 2015-06-29 | Human parathyroid hormone-containing pharmaceutical composition and preparing method and use thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510367315.4A CN106309358A (en) | 2015-06-29 | 2015-06-29 | Human parathyroid hormone-containing pharmaceutical composition and preparing method and use thereof |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN106309358A true CN106309358A (en) | 2017-01-11 |
Family
ID=57721503
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201510367315.4A Pending CN106309358A (en) | 2015-06-29 | 2015-06-29 | Human parathyroid hormone-containing pharmaceutical composition and preparing method and use thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN106309358A (en) |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108159404A (en) * | 2018-01-05 | 2018-06-15 | 北京博康健基因科技有限公司 | Recombinant human parathyroid hormone preparation and preparation method thereof |
| CN110755380A (en) * | 2019-11-04 | 2020-02-07 | 中国人民解放军军事科学院军事医学研究院 | Parathyroid hormone 1-34 nasal spray, preparation method and application thereof |
| CN110917150A (en) * | 2019-12-31 | 2020-03-27 | 北京博康健基因科技有限公司 | PTH freeze-dried preparation and preparation method thereof |
| CN113967249A (en) * | 2021-12-10 | 2022-01-25 | 深圳先进技术研究院 | Application of parathyroid hormone in preparation of medicine or health-care product for treating male depression |
Citations (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0619119A1 (en) * | 1991-12-09 | 1994-10-12 | Asahi Kasei Kogyo Kabushiki Kaisha | Stabilized parathyroid hormone composition |
| CN1281370A (en) * | 1997-12-09 | 2001-01-24 | 伊莱利利公司 | Stabilized teriparatide solutions |
| CN1319003A (en) * | 1998-04-28 | 2001-10-24 | Nps阿尔利克斯公司 | Protein formulations |
| CN101011572A (en) * | 2007-02-02 | 2007-08-08 | 重庆科润生物医药研发有限公司 | Medicinal composition of recombinant human parathormone(1-84) and its preparing process |
| CN101189025A (en) * | 2005-06-03 | 2008-05-28 | 财团法人牧岩生命工学研究所 | Stabilized parathyroid hormone composition comprising parathyroid hormone, buffer and stabilizing agent |
| WO2010151703A1 (en) * | 2009-06-25 | 2010-12-29 | Aegis Therapeutics, Llc | Stabilizing alkylglycoside compositions and methods thereof |
| CN103301058A (en) * | 2013-06-17 | 2013-09-18 | 深圳翰宇药业股份有限公司 | Composition for teriparatide injection, and preparation method and preparation thereof |
-
2015
- 2015-06-29 CN CN201510367315.4A patent/CN106309358A/en active Pending
Patent Citations (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0619119A1 (en) * | 1991-12-09 | 1994-10-12 | Asahi Kasei Kogyo Kabushiki Kaisha | Stabilized parathyroid hormone composition |
| CN1281370A (en) * | 1997-12-09 | 2001-01-24 | 伊莱利利公司 | Stabilized teriparatide solutions |
| CN1319003A (en) * | 1998-04-28 | 2001-10-24 | Nps阿尔利克斯公司 | Protein formulations |
| CN101189025A (en) * | 2005-06-03 | 2008-05-28 | 财团法人牧岩生命工学研究所 | Stabilized parathyroid hormone composition comprising parathyroid hormone, buffer and stabilizing agent |
| CN101011572A (en) * | 2007-02-02 | 2007-08-08 | 重庆科润生物医药研发有限公司 | Medicinal composition of recombinant human parathormone(1-84) and its preparing process |
| WO2010151703A1 (en) * | 2009-06-25 | 2010-12-29 | Aegis Therapeutics, Llc | Stabilizing alkylglycoside compositions and methods thereof |
| CN103301058A (en) * | 2013-06-17 | 2013-09-18 | 深圳翰宇药业股份有限公司 | Composition for teriparatide injection, and preparation method and preparation thereof |
Non-Patent Citations (1)
| Title |
|---|
| 梁文权主编: "《药剂学》", 30 September 2005, 科学技术文献出版社 * |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108159404A (en) * | 2018-01-05 | 2018-06-15 | 北京博康健基因科技有限公司 | Recombinant human parathyroid hormone preparation and preparation method thereof |
| CN110755380A (en) * | 2019-11-04 | 2020-02-07 | 中国人民解放军军事科学院军事医学研究院 | Parathyroid hormone 1-34 nasal spray, preparation method and application thereof |
| CN110917150A (en) * | 2019-12-31 | 2020-03-27 | 北京博康健基因科技有限公司 | PTH freeze-dried preparation and preparation method thereof |
| CN113967249A (en) * | 2021-12-10 | 2022-01-25 | 深圳先进技术研究院 | Application of parathyroid hormone in preparation of medicine or health-care product for treating male depression |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| AU2002349513B2 (en) | Medicinal compositions for nasal absorption | |
| CA1336401C (en) | Intranasal administration of polypeptides in powdered form | |
| KR100854198B1 (en) | 21 muteins of fibroblast growth factor 21 | |
| CN102387784B (en) | Lyophilized recombinant vwf formulations | |
| EP1180368B1 (en) | Freeze dried hgf preparations | |
| JPH04247034A (en) | Drug composition for nose | |
| JP3927248B2 (en) | HGF lyophilized formulation | |
| JP4255515B2 (en) | Stabilized growth hormone formulation and method for producing the same | |
| NO323360B1 (en) | Aqueous pharmaceutical composition containing human growth hormone, histidine and a poloxamer 188, and use thereof in the manufacture of a medicament. | |
| KR20150138428A (en) | Liquid formulation of fsh | |
| CN106309358A (en) | Human parathyroid hormone-containing pharmaceutical composition and preparing method and use thereof | |
| JP2016034958A (en) | Stable mia/cd-rap formulation | |
| EP0809512A1 (en) | Pharmaceutical non inorganic saline solutions for endonasal administration of a calcitonin | |
| WO2001068125A2 (en) | Methods and compositions for the treatment and prevention of erectile dysfunction | |
| IE60649B1 (en) | Mixed crystals of insulin and insulin derivatives, a process for the preparation of these mixed crystals, and pharmaceutical agents containing these mixed crystals | |
| US11077193B2 (en) | Nerve growth factor composition and powder injection | |
| NZ541493A (en) | Use of kahalalide compounds for the manufacture of a medicament for the treatment of psoriasis | |
| KR101095647B1 (en) | Glycoprotein hormone composition | |
| KR101483165B1 (en) | Compositions of menopausal gonadotrophins | |
| JPH05331199A (en) | Lyophilized acidic fibroblast growth factor | |
| JPS60233017A (en) | Use of gonadoliberin and gonadoliberin agonist for treating menopause troubles | |
| WO1995022342A1 (en) | Pharmaceutical formulations of ciliary neurotrophic factor | |
| MXPA03008545A (en) | Pharmaceutical compositions containing human growth hormone. | |
| JPH107586A (en) | Preventive and/or therapeutic agent for disease caused by insulin-like action |
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 | ||
| CB02 | Change of applicant information |
Address after: 610041 South Keyuan Road, Chengdu High-tech Zone, Chengdu, Sichuan Province, No. 88, 10 buildings, 2 floors, 203 Applicant after: Xinlitai (Chengdu) Biotechnology Co., Ltd. Address before: 610041 South Keyuan Road, Chengdu High-tech Zone, Chengdu, Sichuan Province, No. 88, 10 buildings, 2 floors, 203 Applicant before: Chengdu Jinkai Biological Technology Co., Ltd. |
|
| CB02 | Change of applicant information | ||
| RJ01 | Rejection of invention patent application after publication |
Application publication date: 20170111 |
|
| RJ01 | Rejection of invention patent application after publication |