CN1287851C - Ossotide sodium chloride injection and its preparing process - Google Patents
Ossotide sodium chloride injection and its preparing process Download PDFInfo
- Publication number
- CN1287851C CN1287851C CN 03111084 CN03111084A CN1287851C CN 1287851 C CN1287851 C CN 1287851C CN 03111084 CN03111084 CN 03111084 CN 03111084 A CN03111084 A CN 03111084A CN 1287851 C CN1287851 C CN 1287851C
- Authority
- CN
- China
- Prior art keywords
- bone
- sodium chloride
- injection
- peptide
- centrifugal
- 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.)
- Expired - Lifetime
Links
Abstract
The present invention relates to an ossotide sodium chloride injection and a preparation technology thereof. The existing peptide injection mainly contains a polypeptide active substance, the polypeptide active substance is easily polymerized into a macromolecular substance in the process of storage to be separated out to generate antigenicity, and the polymerization of the polypeptide active substance increases with the increase of the concentration of the polypeptide active substance to cause the increase of an anaphylactic reaction in clinical application. The ossotide sodium chloride injection is prepared from ossotide solution, sodium chloride and injection water. The present invention also comprises a preparation method for the injection. The ossotide sodium chloride injection treats hyperplasia osteoarthropathy, rheumatism, rheumatoid arthritis, etc., and can promote fracture recovery.
Description
Technical field: the present invention relates to a kind of Bone Peptide Sodium Chloride Parenteral Solution And Preparing Craft.
Background technology: the main component of bone peptide is a micromolecule polypeptide class material, be to decompose and next little peptide mixer by collagen protein, polymerization forms than macromole voluntarily in preservation, and along with the prolongation of holding time, polymer is separated out and increased, thereby generation antigenicity, its polymerization increases with the rising of peptide matters concentration, thereby causes that the allergy reflection incidence rate in the clinical practice increases, and reaches as high as 0.1%, generally be to begin to occur erythra, fever, hypotension etc. in medication 5-6 days.Because peptide class injection often in the mode of intravenous drip, needs it to be dissolved in the 200ml0.9% sodium chloride injection, causes the secondary pollution of medicine during dead point easily temporarily, influenced the safety that medicine uses thereby produce pyrogen reaction in clinical use.
Summary of the invention: the purpose of this invention is to provide a kind of Bone Peptide Sodium Chloride Parenteral Solution And Preparing Craft.
Above-mentioned purpose realizes by following technical scheme:
Bone-peptide sodium chloride injection, this product is made of bone peptide solution, sodium chloride and water for injection, and its per hundred milliliters contain bone peptide solution share is 10-50ml, and wherein per hundred milliliters contain 0.05-2 gram NaCl.
Above-mentioned bone-peptide sodium chloride injection, its per hundred milliliters contain bone peptide solution share is 10-50ml, contains polypeptides matter 5.0--20mg/ml in the described bone peptide solution, pH value is 3.0-10, produces purple blue with the ninhydrin solution reaction.
A kind of preparation technology of bone-peptide sodium chloride injection, described preparation technology comprises following process: get fetal bovine limb bone, add pure water and extract twice in 100-120 ℃ of hot pressing, each 0.5-2 hour, extracting liquid filtering, left standstill 15-24 hour with HCl adjust pH 3.0-5.5, centrifugal, get supernatant with NaOH adjust pH 8.0-10.0, freezing more than 24 hours at-10～-25 ℃, take out and melt, centrifugal, get supernatant, use the HCl adjust pH to 6.5-7.5, be heated to 70-100 ℃, centrifugal, get supernatant, with molecular weight 5000-10000 membrane ultrafiltration, collect ultrafiltrate, in concentration is 3% sodium chloride solution, add the active carbon of 0.05～0.2%g/ml, boiled filtering decarbonization 5-30 minute, be cooled to room temperature, 0.45 μ m filtering with microporous membrane, the described ultrafiltrate of adding recipe quantity, adjust pH 6.5-7.5, with 22 μ m microporous filter membrane degerming, in 100-115 ℃ of sterilization 30 minutes.
This technical scheme has following beneficial effect:
1. product of the present invention is through fine straining repeatedly, adopt the mode of injection, bone peptide concentration is low, good stability in the process of storage, oligosaccharide, nucleic acid derivative, aminoacid and low-molecular-weight polypeptide are difficult for taking place polymerization, significantly reduce the anaphylaxis incidence rate, avoided producing antigenicity, reduced anaphylaxis in the clinical practice.Simultaneously,, not only alleviated medical personnel's workload, also reduced the contaminated probability of medicine, guaranteed drug safety because the present invention when intravenous drip, need not to be dissolved in 5% glucose injection or the sodium chloride injection again.
2. this product adopts fetal bovine bone as raw material, through pressurization polypeptide composition is wherein extracted, and through the repeated treatments of bronsted lowry acids and bases bronsted lowry, leach impurity timely and make through the membrane ultrafiltration of 5000-10000 molecular weight, its even structure is stable.
3. use certain density charcoal treatment, active adsorption pyrogen and impurity, after taking off charcoal, carry out filtering with microporous membrane once more, then according to the recipe quantity that will dispose, the bone peptide solution that adds high concentration, behind the adjust pH, adopt the microporous filter membrane degerming once more, and carry out high temperature sterilize, carry out high-precision purification process, make the untoward reaction of this product obviously reduce.
4. through Clinical Laboratory, the injection of the bone-peptide sodium chloride of this concentration can obviously reduce untoward reaction, its good stability, and the polymer concentration of sensitinogen is low, and clinical adverse is little, contrasts as follows:
In general injection, having naked eyes can't observed polymer substance, and along with the increase of polymer substance, sensitinogen will increase, so the clinical adverse incidence rate strengthens, and the polymer substance of this product produces few, contrasts as follows:
Get each three batches of the injection of bone peptide solution and this product respectively, 100 every batch are kept at respectively under 20 ℃, 30 ℃, the 40 ℃ conditions, detected at 3,6,9,12,18 months.Adopt high-efficient liquid phase technique to mark thing as macromolecule with ribonuclease A molecular weight 1300.Calculating the macromolecule peak area gross area with the area normalization method is standard with＜5%, is defective greater than it.Assay sees Table 1 and table 2
Table 1 bone peptide solution is as the polymer substance testing result of medicine
| Temperature | Polymer substance disqualification rate % | ||||
| March | June | JIUYUE | December | 18 months | |
| 20℃ 30℃ 40℃ | 1.8 3.5 21.0 | 4.7 5.3 25.3 | 5.9 7.6 30.2 | 8.3 11.2 37.1 | 11.3 20.3 39.5 |
The polymer substance testing result of this product of table 2
| Temperature | Polymer substance disqualification rate %, | ||||
| March | June | JIUYUE | December | 18 months | |
| 20℃ | 0.8 | 1.5 | 2.4 | 2.8 | 3.0 |
| 30℃ 40℃ | 1.0 2.5 | 1.6 3.0 | 2.6 3.1 | 2.9 3.8 | 3.0 4.5 |
Above statistical data shows that this product can obviously reduce polymer substance, because biological preparation is in clinical use.Be difficult to be kept at low temperature environment, at room temperature even be higher than under 20 ℃ the environment, the bone peptide solution of high concentration increase polymer substance in time can obviously increase, and will obviously increase the side effect of medicine in clinical and influence its curative effect.And the bone-peptide sodium chloride injection of this product is a solvent with the normal saline.Polypeptides matter intermolecular distance wherein is bigger, is difficult for polymerization between the molecule, thereby will obviously reduce the appearance of polymer substance, reduces the side reaction of medicine, improves its scope of application in clinical.
Thereby can draw product of the present invention and help the preservation of medicine as a kind of new dosage form, the medicine holding time can obviously prolong, and untoward reaction obviously reduces, and has therefore increased the scope of application of bone peptide, has reduced incidence rate of adverse reaction.
Particularly southern hospital, the most of the time temperature was higher in 1 year, and the condition of preserving medicine does not reach low temperature, often be higher than 20 ℃ even be higher than 30 ℃, the adverse drug reaction incidence rate of therefore a lot of hospitals is higher, and the product that the inventive method is made is not obvious with variation of temperature, can obviously reduce adverse reaction rate thus, so this product also is fit to the southern area use more
Embodiment 1:
Bone-peptide sodium chloride injection, this product is made of bone peptide solution, sodium chloride and water for injection.
Above-mentioned bone-peptide sodium chloride injection, its per hundred milliliters contain bone peptide solution share is 10-50ml, contains polypeptides matter 5.0-20mg/ml in the described bone peptide solution, pH value is 3.0-10, produces purple blue with the ninhydrin solution reaction.Wherein per hundred milliliters contain 0.05-2 gram NaCl, add injection water to 100 milliliter.
Embodiment 2:
Bone-peptide sodium chloride injection, its composition comprises: bone peptide solution 20-50 liter, for example 25 liters, 30 liters, 35 liters, 40 liters, 45 liters, 50 liters or period interval numerical value, add 0.8-1 kilogram NaCl in the described bone peptide solution, add injection water to 100 liter, or abide by this weight-to-volume ratio example and zoom in or out.
Be in above-mentioned per hundred milliliters of bone-peptide sodium chloride injections, to contain 1ml or 2ml or 3ml or 4ml or 5ml, perhaps the bone peptide solution of any numerical value among the 1ml-5ml promptly wherein polypeptides matter greater than 5.0mg/ml.For example
Bone peptide solution 10-50L
Sodium chloride 0.8-1.0kg
Water for injection 100L fill becomes 1000 bottles.
Embodiment 3:
A kind of preparation technology of bone-peptide sodium chloride injection, described preparation technology comprises following process: get fetal bovine limb bone, add pure water and extract twice in 100-120 ℃ of hot pressing, each 0.5-2 hour, extracting liquid filtering, left standstill 15-24 hour with HCl adjust pH 3.0-5.5, centrifugal, get supernatant with NaOH adjust pH 8.0-10.0, freezing more than 24 hours at-10～-25 ℃, take out and melt, centrifugal, get supernatant, use the HCl adjust pH to 6.5-7.5, be heated to 70-100 ℃, centrifugal, get supernatant, with molecular weight 5000-10000 membrane ultrafiltration, collect ultrafiltrate, in concentration is 3% sodium chloride solution, add the active carbon of 0.05～0.2%g/ml, boiled filtering decarbonization 5-30 minute, be cooled to room temperature, 0.45 μ m filtering with microporous membrane, the described ultrafiltrate of adding recipe quantity, adjust pH 6.5-7.5, with 22 μ m microporous filter membrane degerming, in 100-115 ℃ of sterilization 30 minutes.
Embodiment 3:
Method of the present invention: get fetal bovine limb bone 32kg, add the 40L pure water, 105 ℃ were extracted 1 hour in the high pressure steam sterilization cabinet.Filter, get filtrate, add 3MHCl solution 510ml (if adopt other concentration, available mol ratio converts), recording pH value behind the mix homogeneously is 4.10.The bone slag adds the pure water of 40L again, and 105 ℃ were extracted 1 hour in the high pressure steam sterilization cabinet.Filter, get filtrate.
Add 3MHCl solution 420ml (if adopt other concentration, available mol ratio converts), mix homogeneously records pH value is 4.32..Leave standstill 20 hours, centrifugal, obtain supernatant 70250ml.
Get supernatant, add down 3MNaOH solution 830ml (if adopt other concentration, available mol ratio converts) constantly whisking, recording pH value is 8.92.-18 ℃ freezing more than 24 hours, take out, melt,
Under agitation add 3MHCl solution 32ml (if adopt other concentration, available mol ratio converts), recording pH value is 6.93, is heated to 80 ℃, centrifugalize, film with molecular weight 8000 carries out ultrafiltration, collect ultrafiltrate, get the high dense bone peptide solution of 61.10L, after testing, content of peptides wherein is 6.50mg/ml, and is standby.
Take by weighing sodium chloride 2700g, add the injection water to 90L, stirring and dissolving is made into 3% sodium chloride solution, adds the injection-use activated carbon of 90g, stirs evenly, and is heated to boiling, keeps filtering decarbonization, fine straining 15 minutes.Sodium chloride solution with 3% and 60L are high, and dense bone peptide solution mixes, adds water for injection to 300L, pull even, the microporous filter membrane fine straining of mistake 0.22 μ m.The content of peptides that records wherein is 1.30mg/ml, and sodium chloride content is 8.79mg/ml, and the pH value of this moment is 6.95, fill, was sterilized 30 minutes for 110 ℃ by 100 milliliters every bottle, be finished product of the present invention after the assay was approved, each one bottle of general clinical use should be used according to doctor's advice.
Claims (3)
1. bone-peptide sodium chloride injection, it is characterized in that: this product is by bone peptide solution, sodium chloride and water for injection constitute, its each hundred milliliters contain bone peptide solution share is 10-50ml, the preparation technology of described bone peptide solution comprises following process: get fetal bovine limb bone, add pure water and extract twice in 100-120 ℃ of hot pressing, each 0.5-2 hour, extracting liquid filtering, left standstill 15-24 hour with HCl adjust pH 3.0-5.5, centrifugal, get supernatant with NaOH adjust pH 8.0-10.0, freezing more than 24 hours at-10～-25 ℃, take out and melt, centrifugal, get supernatant, use the HCl adjust pH to 6.5-7.5, be heated to 70-100 ℃, centrifugal, get supernatant, with molecular weight 5000-10000 membrane ultrafiltration, collect ultrafiltrate, make bone peptide solution.
2. bone-peptide sodium chloride injection according to claim 1, it is characterized in that: it is 10-50ml that described bone-peptide sodium chloride injection contains bone peptide solution share for each hundred milliliters, contain polypeptides matter 5.0--20mg/ml in the described bone peptide solution, pH value is 3.0-10, and the present invention and ninhydrin solution reaction produce purple blue.
3. the preparation technology of a bone-peptide sodium chloride injection, described preparation technology comprises following process: get fetal bovine limb bone, add pure water and extract twice in 100-120 ℃ of hot pressing, each 0.5-2 hour, extracting liquid filtering, 3.0-5.5 leaves standstill 15-24 hour with the HCl adjust pH, and is centrifugal, gets supernatant NaOH adjust pH 8.0-10.0, freezing more than 24 hours at-10～-25 ℃, take out and melt, centrifugal, get supernatant, with the HCl adjust pH to 6.5-7.5, be heated to 70-100 ℃, centrifugal, get supernatant, with molecular weight 5000-10000 membrane ultrafiltration, collect ultrafiltrate, make bone peptide solution, it is characterized in that: the active carbon that in concentration is 3% sodium chloride solution, adds 0.05～0.2%g/ml, boiled 5-30 minute, filtering decarbonization is cooled to room temperature, with 0.45 μ m filtering with microporous membrane, the described ultrafiltrate that adds recipe quantity, adjust pH 6.5-7.5 is with 22 μ m microporous filter membrane degerming, in 100～115 ℃ of sterilizations 30 minutes.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 03111084 CN1287851C (en) | 2003-02-26 | 2003-02-26 | Ossotide sodium chloride injection and its preparing process |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 03111084 CN1287851C (en) | 2003-02-26 | 2003-02-26 | Ossotide sodium chloride injection and its preparing process |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN1524573A CN1524573A (en) | 2004-09-01 |
| CN1287851C true CN1287851C (en) | 2006-12-06 |
Family
ID=34283373
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN 03111084 Expired - Lifetime CN1287851C (en) | 2003-02-26 | 2003-02-26 | Ossotide sodium chloride injection and its preparing process |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN1287851C (en) |
Families Citing this family (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1318085C (en) * | 2005-06-09 | 2007-05-30 | 赵红梅 | Ossotide injection and preparation method thereof |
| CN1939343B (en) * | 2006-10-13 | 2010-05-19 | 俞嘉林 | Bone-peptide sodium chloride injection and its making method |
| CN100457178C (en) * | 2007-05-25 | 2009-02-04 | 黑龙江省珍宝岛制药有限公司 | Process for preparing bone peptide injection |
| CN102920994B (en) * | 2012-11-29 | 2013-11-06 | 罗诚 | Pharmaceutical composition containing animal bone polypeptide |
| CN103041366B (en) * | 2012-12-25 | 2014-06-18 | 黑龙江珍宝岛药业股份有限公司 | Bone peptide composition and preparation method thereof |
| CN109331169A (en) * | 2018-09-30 | 2019-02-15 | 派生特（福州）生物科技有限公司 | A kind of sheep bone peptide oral liquid and preparation method thereof |
-
2003
- 2003-02-26 CN CN 03111084 patent/CN1287851C/en not_active Expired - Lifetime
Also Published As
| Publication number | Publication date |
|---|---|
| CN1524573A (en) | 2004-09-01 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN102166360B (en) | Ibuprofen intravenously administrable preparation and preparation method thereof | |
| EP2209814B1 (en) | Dilute filtration sterilization process for viscoelastic biopolymers | |
| CA1099639A (en) | High calorie solutions of low molecular weight glucose polymer mixtures useful for intravenous administration | |
| CN1068778C (en) | Novel drug composition for treating and curing and its preparing method | |
| CN103550143B (en) | A kind of preparation method of levetiracetam injection | |
| CN1287851C (en) | Ossotide sodium chloride injection and its preparing process | |
| CN102626409B (en) | A kind of pharmaceutical composition containing 18 seed amino acids | |
| WO2022222630A1 (en) | Multiple electrolytes injection and preparation method therefor | |
| CN102525893B (en) | Phenylephrine hydrochloride injection and preparation process thereof | |
| CN111939121B (en) | Heparin sodium tube-sealing injection and preparation method thereof | |
| CN1218747C (en) | Medicinal use of agkistrodon acutus thrombase for treating hemorrhagic disease | |
| CN1244403A (en) | Preparation of isotomic Shengmei injecta | |
| CN1682736A (en) | Gatifloxacin lactate injection and its preparing method | |
| CN1233414C (en) | Muscular amino acid and peptide nucleoside powder injection and its preparation method | |
| CN102166200A (en) | Freeze-drying composition containing cerebroprotein hydrolysates and preparation method of freeze-drying composition | |
| CN101703466A (en) | Borneol injection and preparation method thereof | |
| CN102716108A (en) | Ibuprofen arginine sodium chloride injection as well as preparation method and use thereof | |
| CN110693822A (en) | Ibuprofen injection and preparation method thereof | |
| Najari et al. | Compatibility of commonly used bone marrow transplant drugs during Y-site delivery | |
| CN1468600A (en) | Prepn process of glucose injection of Doxofylline | |
| CN101664385B (en) | Ibutilide fumarate injection and preparation method thereof | |
| CN101756895B (en) | Polyene phosphatidyl choline intravenous preparation and preparation method thereof | |
| CN111265594A (en) | Medicinal preparation for repairing wound and preparation method thereof | |
| CN110314132B (en) | Ornithine aspartate injection and preparation method thereof | |
| CN108926703A (en) | Ossotide glucose injection |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| EE01 | Entry into force of recordation of patent licensing contract |
Assignee: Heilongjiang Jiang Shi Pharmaceutical Co.,Ltd. Assignor: Jiang Weishi Contract fulfillment period: 2008.8.18 to 2018.8.18 Contract record no.: 2008230000002 Denomination of invention: Ossotide sodium chloride injection and its preparing process Granted publication date: 20061206 License type: Exclusive license Record date: 20080923 |
|
| LIC | Patent licence contract for exploitation submitted for record |
Free format text: EXCLUSIVE LICENSE; TIME LIMIT OF IMPLEMENTING CONTACT: 2008.8.18 TO 2018.8.18; CHANGE OF CONTRACT Name of requester: HEILONGJIANG JIANGSHI PHARMACEUTICAL CO., LTD. Effective date: 20080923 |
|
| TR01 | Transfer of patent right |
Effective date of registration: 20210208 Address after: No.2, Weihai Road, Pingfang economic and Technological Development Zone, Harbin, Heilongjiang, 150096 Patentee after: Heilongjiang Jiang Shi Pharmaceutical Co.,Ltd. Address before: 150096 No. 2 Weihai Road, cottage District, Heilongjiang, Harbin Patentee before: Jiang Weishi |
|
| TR01 | Transfer of patent right | ||
| CX01 | Expiry of patent term |
Granted publication date: 20061206 |
|
| CX01 | Expiry of patent term |