CN107007822A - A kind of pharmaceutical composition containing plain 2 analogs of recombinant human relaxin and preparation method thereof - Google Patents
A kind of pharmaceutical composition containing plain 2 analogs of recombinant human relaxin and preparation method thereof Download PDFInfo
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- CN107007822A CN107007822A CN201710057882.9A CN201710057882A CN107007822A CN 107007822 A CN107007822 A CN 107007822A CN 201710057882 A CN201710057882 A CN 201710057882A CN 107007822 A CN107007822 A CN 107007822A
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- 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
- A61K38/2221—Relaxins
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- 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
- A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
- A61K47/12—Carboxylic acids; Salts or anhydrides thereof
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- 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
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- 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
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Abstract
The invention provides a kind of pharmaceutical composition containing plain 2 analogs of recombinant human relaxin and preparation method thereof.Specifically, comprising plain 2 analogs of recombinant human relaxin and at least one buffer in the injection formula, wherein described buffer is selected from least one of citrate, succinate, tartrate, gluconate, lactate, acetate.The plain 2 similar composition injections of recombinant human relaxin of the present invention have the characteristics of having good stability, be easy to industrialized production.
Description
Technical field
The invention belongs to field of pharmaceutical preparations, and in particular to being available for of a kind of plain -2 analogs containing recombinant human relaxin is administered to
The pharmaceutical preparation of medicine, said preparation has the characteristics of having good stability, be easy to industry amplification.
Background technology
Relaxain (Relaxin abbreviation RLX) is a kind of polypeptide hormone, its by mammal ovarian secretion.Have in vivo
There are different physiological roles, including relaxation Cooper's ligament, suppression uterine contractile, softening cervix etc..Nineteen twenty-six, relaxain by
Frederick Hisaw have found first.70-80 ages in 20th century, relaxain is considered as a kind of dichain proteins matter.Relaxain
Structure is similar to insulin.Relaxain family includes 7 members, is mainly wherein RLN2 (Relaxin-2) in human body.
A series of researchs in recent years find that RLN2 has significant therapeutic effect, energy to angiocardiopathies such as heart failure
Expansion body systemic vascular is reached, renal blood vessels is expanded and increases arterial compliance.Relevant clinical experimental study shows that people relaxes
Element -2 shows good curative effect and peace in the treatment for acute heart failure (Acute Heart Failure, AHF)
Quan Xing.
US5166191, which discloses relaxin, to be used to treat angiocardiopathy especially heart failure.CN1052655 is disclosed
The influence of pH value of solution and ionic strength to relaxin stability, and disclose a kind of liquid preparation of relaxin, the liquid preparation
Suitable concentration be about 1.0mg/mL, but the peptide injection concentration that fails to solve to relax increase caused by preparation stability significantly reduce
The problem of.CN102133200 discloses the freeze-dried powder preparation and its preparation technology of a kind of relaxin.But freeze-dried powder preparation is in application
It is preceding to need to redissolve operation, so as to be delayed the best occasion for the treatment of acute heart failure.CN103768584 is disclosed containing cow's serum
Albumin or human serum albumins, buffer salt, sodium chloride, PEG200 or PEG400 relaxain parenteral solution.
WO2015067113 discloses a kind of plain -2 analogs of recombinant human relaxin of particular sequence, and it includes A chains and B chains,
This analog can be in the inner protein folding for completing relaxain precursor of eukaryotic expression system (cell), digestion, and is secreted into hair
In zymotic fluid.Its biological activity is higher than wild type relaxain more than 2 times, and concrete structure sequence is as follows：
Wherein B chains (DB14) DSWMEEVIKLCGRDLVRAQIAICGMSTWS, A chains (DA1)
DLYSALANKCCHVGCTKRSLARFC, passes through disulfide bond between the two.
As polypeptide drug, recombinant human relaxin -2 analogs of element have the characteristics of such medicine is universal, i.e. oral bio
Availability is low, is easily destroyed by various enzymes degraded in vivo, and stability is low, degradable and denaturation, at the same with other protein
Polypeptide drug is similar, and the analog of recombinant human relaxain -2 is unsuitable for being administered orally.Therefore it provides one kind is stable, be difficult drop
Solution and the analog ejection preparation of recombinant human relaxain -2 of deformation, are a kind of challenges for those skilled in the art.
The content of the invention
It is an object of the invention to provide a kind of intravenously administrable system of plain -2 analogs of recombinant human relaxin having good stability
Agent, and the preparation technology of said preparation is simple, is suitable for industrialized production.
The present invention provides plain -2 analogue medicinal compositions of recombinant human relaxin for being available for injection, contains active component recombined human
The analog of relaxain -2 and at least one buffer.
Plain -2 analogs of recombinant human relaxin of the present invention, include A chains and B chains, between the two by disulfide bond, A
The amino acid sequence of chain and B chains is as follows：
B chains (DB14)DSWMEEVIKLCGRDLVRAQIAICGMSTWSSEQ ID NO:1
A chains (DA1)DLYSALANKCCHVGCTKRSLARFC SEQ ID NO:2
Plain -2 analog concrete structures of recombinant human relaxin that A chains are formed after being connected with B chains are as follows：
The concentration range of plain -2 analogs of pharmaceutical composition recombinant human relaxin of the present invention is 1-4mg/ml, preferably 1-
2mg/ml, more excellent is 1-1.5mg/ml.
Buffer of the present invention can be for citrate (for example：The mixture of the sodium of citric acid one and disodium, citric acid-
The mixture of citric acid trisodium salt, mixture of citric acid-citric acid mono-sodium salt etc.), succinate is (for example：Butanedioic acid-amber
The mixture of sour mono-sodium salt, butanedioic acid-sodium hydroxide mixture etc.), tartrate is (for example：Tartaric acid-sodiotartrate it is mixed
Compound, tartaric acid-sodium hydroxide mixture etc.), acetate (mixture of acetic acid and sodium acetate), malate, gluconate,
At least one of lactate.Here, preferably citric acid salt.The pharmaceutical composition of the present invention, its pH scope is 4.0-7.0, excellent
Elect 4.0-6.0 as, more excellent is 4.5-5.5.
Furthermore, the present invention provides a kind of pharmaceutical composition, containing plain -2 analogs of recombinant human relaxin and citric acid -
- 2 analog concentration of recombinant human relaxin element are 0.5~1.5mg/ml, pharmaceutical composition in sodium citrate buffer, pharmaceutical composition
PH be maintained at 5.0 or so.
Also contain appropriate isotonic regulator in pharmaceutical composition of the present invention, prescription is given in favor of parenteral
Formula, especially venoclysis.Described isotonic regulator can be selected from sodium chloride or glucose, preferably sodium chloride.
Pharmaceutical composition of the present invention, its osmolarity ranges are 200-300mOsm/kg, preferably 240-260mOsm/
kg。
Before clinical administration, the pharmaceutical composition that the present invention is provided need to be diluted with a kind of aqueous diluent, wherein institute
The aqueous diluent stated may be selected from water for injection, physiological saline, preferably 5% glucose solution, physiological saline.
Present invention also offers a kind of method for preparing plain -2 analogue compositions of the recombinant human relaxin, including following step
Suddenly：
1) stabilizing solution is prepared：The sta-salt for weighing recipe quantity adds the water for injection of about 90% recipe quantity, stirs at room temperature
Dissolving, adds appropriate isotonic regulator,；
2) into above-mentioned solution, plain -2 analogs of recombinant human relaxin of recipe quantity is added, are stirred at room temperature；
3) it is fixed molten：Benefit injects water to final volume, stirs at room temperature, with well mixed.
In order to obtain the pharmaceutical composition for meeting parenteral solution standard, the above method also contains 4) by above-mentioned decoction through 0.22 μm
Filtering with microporous membrane after, the step of obtaining sterile liquid medicine.In order to commercial distribution need above-mentioned gained sterile liquid medicine is further
Cillin bottle is distributed into, lid is rolled in tamponade.
Embodiment
Following examples are to illustrate invention, the scope of the present invention is not limited in any way.
Embodiment 1
Raw material proportioning：
| Recombinant human relaxin -2 analogs of element | 100mg |
| Citric acid | 69.3mg |
| Sodium citrate | 197.1mg |
| Sodium chloride | 724.7mg |
| Water for injection | 100ml |
| PH value | 5.0 |
Preparation method is as follows：
The citrate of recipe quantity is weighed, the water for injection of about 90% recipe quantity is added, at room temperature stirring and dissolving；To above-mentioned
In solution, plain -2 analogs of recombinant human relaxin of recipe quantity are added, at room temperature stirring and dissolving；Benefit injects water to final body
Product, is stirred at room temperature, with well mixed；By above-mentioned decoction after 0.22 μm of filtering with microporous membrane, sterile liquid medicine, Ran Houfen are obtained
Load cillin bottle, tamponade is rolled lid, produced.
Embodiment 2
Raw material proportioning：
Preparation method is as follows：
The acetate of recipe quantity is weighed, the water for injection of about 90% recipe quantity is added, at room temperature stirring and dissolving；To above-mentioned molten
In liquid, plain -2 analogs of recombinant human relaxin of recipe quantity are added, at room temperature stirring and dissolving；Benefit injects water to final volume,
Stir at room temperature, with well mixed；By above-mentioned decoction after 0.22 μm of filtering with microporous membrane, sterile liquid medicine is obtained, is then dispensed
Enter cillin bottle, tamponade is rolled lid, produced.
Embodiment 3
Raw material proportioning：
| Recombinant human relaxin -2 analogs of element | 100mg |
| Tartaric acid | 82.5mg |
| Sodium tartrate | 140.5mg |
| Sodium chloride | 724.7mg |
| Water for injection | 100ml |
| PH value | 5.0 |
Preparation method is as follows：
The tartrate of recipe quantity is weighed, the water for injection of about 90% recipe quantity is added, at room temperature stirring and dissolving；To above-mentioned
In solution, plain -2 analogs of recombinant human relaxin of recipe quantity are added, at room temperature stirring and dissolving；Benefit injects water to final body
Product, is stirred at room temperature, with well mixed；By above-mentioned decoction after 0.22 μm of filtering with microporous membrane, sterile liquid medicine, Ran Houfen are obtained
Load cillin bottle, tamponade is rolled lid, produced.
Embodiment 4
Raw material proportioning：
| Recombinant human relaxin -2 analogs of element | 100mg |
| Butanedioic acid | 52.0mg |
| Sodium succinate | 90.7mg |
| Sodium chloride | 724.7mg |
| Water for injection | 100ml |
| PH value | 5.0 |
Preparation method is as follows：
The succinate of recipe quantity is weighed, the water for injection of about 90% recipe quantity is added, at room temperature stirring and dissolving；To above-mentioned
In solution, plain -2 analogs of recombinant human relaxin of recipe quantity are added, at room temperature stirring and dissolving；Benefit injects water to final body
Product, is stirred at room temperature, with well mixed；By above-mentioned decoction after 0.22 μm of filtering with microporous membrane, sterile liquid medicine, Ran Houfen are obtained
Load cillin bottle, tamponade is rolled lid, produced.
According to embodiment 1 to the similar composition injection of the Prepare restructuring RLN2 of embodiment 4, and respectively under the conditions of 30 DEG C
14d is placed, is sampled in 0,7,14d, the relevant material of decoction is determined using RP-HPLC method (HPLC), its is investigated steady
It is qualitative.Study on the stability result is as follows：
The embodiment 1 of table 1 is to the formulation samples stability of embodiment 4
The result of table 1 shows that plain -2 similar composition injections of recombinant human relaxin in embodiment 1 are still protected after 30 DEG C are placed 14d
It is fixed to keep steady, and the less stable of the preparation prepared by embodiment 2,3,4.The result shows use the preferred of citrate
Prescription has more preferable stability.
Embodiment 5
Raw material proportioning：
| Recombinant human relaxin -2 analogs of element | 10mg |
| Citric acid | 69.3mg |
| Sodium citrate | 197.1mg |
| Sodium chloride | 724.7mg |
| Water for injection | 100ml |
| PH value | 5.0 |
Preparation method is as follows：
The citrate of recipe quantity is weighed, the water for injection of about 90% recipe quantity is added, at room temperature stirring and dissolving；To above-mentioned
In solution, plain -2 analogs of recombinant human relaxin of recipe quantity are added, at room temperature stirring and dissolving；Benefit injects water to final body
Product, is stirred at room temperature, with well mixed；By above-mentioned decoction after 0.22 μm of filtering with microporous membrane, sterile liquid medicine, Ran Houfen are obtained
Load cillin bottle, tamponade is rolled lid, produced.
Embodiment 6
Raw material proportioning：
| Recombinant human relaxin -2 analogs of element | 50mg |
| Citric acid | 69.3mg |
| Sodium citrate | 197.1mg |
| Sodium chloride | 724.7mg |
| Water for injection | 100ml |
| PH value | 5.0 |
Preparation method is as follows：
The citrate of recipe quantity is weighed, the water for injection of about 90% recipe quantity is added, at room temperature stirring and dissolving；To above-mentioned
In solution, plain -2 analogs of recombinant human relaxin of recipe quantity are added, at room temperature stirring and dissolving；Benefit injects water to final body
Product, is stirred at room temperature, with well mixed；By above-mentioned decoction after 0.22 μm of filtering with microporous membrane, sterile liquid medicine, Ran Houfen are obtained
Load cillin bottle, tamponade is rolled lid, produced.
Embodiment 7
Raw material proportioning：
| Recombinant human relaxin -2 analogs of element | 200mg |
| Citric acid | 69.3mg |
| Sodium citrate | 197.1mg |
| Sodium chloride | 724.7mg |
| Water for injection | 100ml |
| PH value | 5.0 |
Preparation method is as follows：
The citrate of recipe quantity is weighed, the water for injection of about 90% recipe quantity is added, at room temperature stirring and dissolving；To above-mentioned
In solution, plain -2 analogs of recombinant human relaxin of recipe quantity are added, at room temperature stirring and dissolving；Benefit injects water to final body
Product, is stirred at room temperature, with well mixed；By above-mentioned decoction after 0.22 μm of filtering with microporous membrane, sterile liquid medicine, Ran Houfen are obtained
Load cillin bottle, tamponade is rolled lid, produced.
Embodiment 8
Raw material proportioning：
| Recombinant human relaxin -2 analogs of element | 400mg |
| Citric acid | 69.3mg |
| Sodium citrate | 197.1mg |
| Sodium chloride | 724.7mg |
| Water for injection | 100ml |
| PH value | 5.0 |
Preparation method is as follows：
The citrate of recipe quantity is weighed, the water for injection of about 90% recipe quantity is added, at room temperature stirring and dissolving；To above-mentioned
In solution, plain -2 analogs of recombinant human relaxin of recipe quantity are added, at room temperature stirring and dissolving；Benefit injects water to final body
Product, is stirred at room temperature, with well mixed；By above-mentioned decoction after 0.22 μm of filtering with microporous membrane, sterile liquid medicine, Ran Houfen are obtained
Load cillin bottle, tamponade is rolled lid, produced.
According to embodiment 1 and the similar composition injection of the Prepare restructuring RLN2 of embodiment 5,6,7,8, and respectively at 30 DEG C
Under the conditions of place 14d, in 0,7,14d samplings, the relevant material of decoction is determined using RP-HPLC method (HPLC), is examined
Examine its stability.Study on the stability result is as follows：
The embodiment 1 of table 2 and the formulation samples stability of embodiment 5,6,7,8
The result of table 2 shows that plain -2 similar composition injections of recombinant human relaxin in embodiment 1 are still protected after 30 DEG C are placed 14d
It is fixed to keep steady, and the less stable of the preparation prepared by embodiment 5,6,7,8.The result shows main ingredient concentration is 1mg/ml
Optimizing prescriptions there is more preferable stability.
Embodiment 9
Raw material proportioning：
| Recombinant human relaxin -2 analogs of element | 100mg |
| Citric acid | 138.7mg |
| Sodium citrate | 100.0mg |
| Sodium chloride | 724.7mg |
| Water for injection | 100ml |
| PH value | 4.0 |
Preparation method is as follows：
The citrate of recipe quantity is weighed, the water for injection of about 90% recipe quantity is added, at room temperature stirring and dissolving；To above-mentioned
In solution, plain -2 analogs of recombinant human relaxin of recipe quantity are added, at room temperature stirring and dissolving；Benefit injects water to final body
Product, is stirred at room temperature, with well mixed；By above-mentioned decoction after 0.22 μm of filtering with microporous membrane, sterile liquid medicine, Ran Houfen are obtained
Load cillin bottle, tamponade is rolled lid, produced.
Embodiment 10
Raw material proportioning：
| Recombinant human relaxin -2 analogs of element | 100mg |
| Citric acid | 109.3mg |
| Sodium citrate | 141.2mg |
| Sodium chloride | 724.7mg |
| Water for injection | 100ml |
| PH value | 4.5 |
Preparation method is as follows：
The citrate of recipe quantity is weighed, the water for injection of about 90% recipe quantity is added, at room temperature stirring and dissolving；To above-mentioned
In solution, plain -2 analogs of recombinant human relaxin of recipe quantity are added, at room temperature stirring and dissolving；Benefit injects water to final body
Product, is stirred at room temperature, with well mixed；By above-mentioned decoction after 0.22 μm of filtering with microporous membrane, sterile liquid medicine, Ran Houfen are obtained
Load cillin bottle, tamponade is rolled lid, produced.
Embodiment 11
Raw material proportioning：
| Recombinant human relaxin -2 analogs of element | 100mg |
| Citric acid | 56.7mg |
| Sodium citrate | 214.7mg |
| Sodium chloride | 724.7mg |
| Water for injection | 100ml |
| PH value | 5.5 |
Preparation method is as follows：
The citrate of recipe quantity is weighed, the water for injection of about 90% recipe quantity is added, at room temperature stirring and dissolving；To above-mentioned
In solution, plain -2 analogs of recombinant human relaxin of recipe quantity are added, at room temperature stirring and dissolving；Benefit injects water to final body
Product, is stirred at room temperature, with well mixed；By above-mentioned decoction after 0.22 μm of filtering with microporous membrane, sterile liquid medicine, Ran Houfen are obtained
Load cillin bottle, tamponade is rolled lid, produced.
Embodiment 12
Raw material proportioning：
| Recombinant human relaxin -2 analogs of element | 100mg |
| Citric acid | 39.9mg |
| Sodium citrate | 238.2mg |
| Sodium chloride | 724.7mg |
| Water for injection | 100ml |
| PH value | 6.0 |
Preparation method is as follows：
The citrate of recipe quantity is weighed, the water for injection of about 90% recipe quantity is added, at room temperature stirring and dissolving；To above-mentioned
In solution, plain -2 analogs of recombinant human relaxin of recipe quantity are added, at room temperature stirring and dissolving；Benefit injects water to final body
Product, is stirred at room temperature, with well mixed；By above-mentioned decoction after 0.22 μm of filtering with microporous membrane, sterile liquid medicine, Ran Houfen are obtained
Load cillin bottle, tamponade is rolled lid, produced.
Embodiment 13
Raw material proportioning：
| Recombinant human relaxin -2 analogs of element | 100mg |
| Citric acid | 14.7mg |
| Sodium citrate | 273.5mg |
| Sodium chloride | 724.7mg |
| Water for injection | 100ml |
| PH value | 7.0 |
Preparation method is as follows：
The citrate of recipe quantity is weighed, the water for injection of about 90% recipe quantity is added, at room temperature stirring and dissolving；To above-mentioned
In solution, plain -2 analogs of recombinant human relaxin of recipe quantity are added, at room temperature stirring and dissolving；Benefit injects water to final body
Product, is stirred at room temperature, with well mixed；By above-mentioned decoction after 0.22 μm of filtering with microporous membrane, sterile liquid medicine, Ran Houfen are obtained
Load cillin bottle, tamponade is rolled lid, produced.
According to embodiment 1 and the similar composition injection of the Prepare restructuring RLN2 of embodiment 9,10,11,12,13, and respectively
14d is placed under the conditions of 30 DEG C, is sampled in 0,7,14d, uses RP-HPLC method (HPLC) to determine the relevant of decoction
Material, investigates its stability.Study on the stability result is as follows：
The embodiment 1 of table 3 and the formulation samples stability of embodiment 9,10,11,12,13
The result of table 3 shows that plain -2 similar composition injections of recombinant human relaxin in embodiment 1 are still protected after 30 DEG C are placed 14d
It is fixed to keep steady, and the less stable of the preparation prepared by embodiment 9,10,11,12,13.It is excellent the result shows pH5.0
Select prescription that there is more preferable stability.
Sequence table
<110>Hengrui Medicine Co., Ltd., Jiangsu Prov.
<120>A kind of pharmaceutical composition containing plain -2 analogs of recombinant human relaxin and preparation method thereof
<130> 370016CG-360030
<160> 2
<170> PatentIn version 3.3
<210> 1
<211> 29
<212> PRT
<213>Artificial sequence
<220>
<223>People's relaxain analog B chains
<400> 1
Asp Ser Trp Met Glu Glu Val Ile Lys Leu Cys Gly Arg Asp Leu Val
1 5 10 15
Arg Ala Gln Ile Ala Ile Cys Gly Met Ser Thr Trp Ser
20 25
<210> 2
<211> 24
<212> PRT
<213>Artificial sequence
<220>
<223>People's relaxain analog A chains
<400> 2
Asp Leu Tyr Ser Ala Leu Ala Asn Lys Cys Cys His Val Gly Cys Thr
1 5 10 15
Lys Arg Ser Leu Ala Arg Phe Cys
20
Claims (12)
1. a kind of plain -2 analogue medicinal compositions of recombinant human relaxin for being available for injection, containing plain -2 analogs of recombinant human relaxin and
At least one buffer.
2. pharmaceutical composition according to claim 1, it is characterised in that plain -2 analogs of the recombinant human relaxin include A chains
With B chains, the amino acid sequence of the A chains and B chains is as follows：
B chains DSWMEEVIKLCGRDLVRAQIAICGMSTWS
A chains DLYSALANKCCHVGCTKRSLARFC.
3. pharmaceutical composition according to claim 1, it is characterised in that plain -2 analogs of the recombinant human relaxin are in medicine
Concentration in composition is 0.1~4mg/ml, preferably 0.5~2mg/ml, and more excellent is 0.5~1.5mg/ml.
4. pharmaceutical composition according to claim 1 or 2, wherein the buffer is selected from citrate, succinate, wine
At least one of stone hydrochlorate, gluconate, lactate, acetate, preferably citrate.
5. pharmaceutical composition according to claim 1, it is characterised in that the pH of described pharmaceutical composition is maintained at 4.0~
7.0, preferably 4.0~6.0, more excellent is 4.5~5.5.
6. pharmaceutical composition according to claim 4, it is characterised in that the buffer is citric acid-sodium citrate.
7. pharmaceutical composition according to claim 6, it is characterised in that plain -2 analogs of the recombinant human relaxin are in medicine
Concentration in composition is 0.5~1.5mg/ml, and the pH of described pharmaceutical composition is maintained at 5.0.
8. the pharmaceutical composition according to claim any one of 1-7, it is characterised in that also including isotonic regulator, described etc.
Ooze conditioning agent and be selected from sodium chloride or glucose, preferably sodium chloride.
9. the pharmaceutical composition according to claim any one of 1-8, it is characterised in that the osmotic pressure model of the pharmaceutical composition
Enclose for 200-300mOsm/kg, preferably 240-260mOsm/kg.
10. the method for any one of claim 1-9 described pharmaceutical composition is prepared, comprising：
1) stabilizing solution is prepared：The buffer for weighing recipe quantity adds the water for injection of about 90% recipe quantity, at room temperature stirring and dissolving,
Add appropriate isotonic regulator；
2) into above-mentioned solution, plain -2 analogs of recombinant human relaxin of recipe quantity is added, are stirred at room temperature；
3) it is fixed molten：Benefit injects water to final volume, stirs at room temperature, with well mixed.
11. method according to claim 10, it is characterised in that the methods described also filtering with microporous membrane containing 0.22 μm is removed
Bacterium step.
12. a kind of method for preparing the solution for venoclysis, including：There is provided and contain drug regimen described in claim 1-11
Thing, adds aqueous diluent and forms a kind of solution reconstituted, the aqueous diluent may be selected from water for injection, physiology salt
Water, preferably 5% glucose solution, physiological saline.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610056528 | 2016-01-27 | ||
| CN201610056528X | 2016-01-27 |
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| CN107007822A true CN107007822A (en) | 2017-08-04 |
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|---|---|---|---|---|
| CN1035619A (en) * | 1988-02-26 | 1989-09-20 | 基因技术公司 | Human relaxin formulation |
| CN102133200A (en) * | 2011-03-16 | 2011-07-27 | 济南环肽医药科技有限公司 | Human relaxin-2 lyophilized powder preparation for injection |
| CN103768584A (en) * | 2014-02-10 | 2014-05-07 | 济南环肽医药科技有限公司 | Relaxin injection |
| CN104870470A (en) * | 2013-11-07 | 2015-08-26 | 上海恒瑞医药有限公司 | Human relaxin analogue, pharmaceutical composition of same, and pharmaceutical application of same |
| CN104922661A (en) * | 2014-03-20 | 2015-09-23 | 深圳翰宇药业股份有限公司 | Pharmaceutical composition containing serelaxin and preparation method thereof |
-
2017
- 2017-01-23 CN CN201710057882.9A patent/CN107007822A/en active Pending
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| CN104922661A (en) * | 2014-03-20 | 2015-09-23 | 深圳翰宇药业股份有限公司 | Pharmaceutical composition containing serelaxin and preparation method thereof |
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