CN101062403A - Process for preparing bone peptide injection - Google Patents
Process for preparing bone peptide injection Download PDFInfo
- Publication number
- CN101062403A CN101062403A CNA2007100996296A CN200710099629A CN101062403A CN 101062403 A CN101062403 A CN 101062403A CN A2007100996296 A CNA2007100996296 A CN A2007100996296A CN 200710099629 A CN200710099629 A CN 200710099629A CN 101062403 A CN101062403 A CN 101062403A
- Authority
- CN
- China
- Prior art keywords
- injection
- bone peptide
- adjust
- add
- bone
- 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
Landscapes
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Abstract
The invention provides a process for preparing bone peptide injection, which is prepared from fresh or freeze pig's or cow's limbs through steps of high pressure extracting, defatting, acid processing, alcohol depositing, alkali treating and hyperfiltrating.
Description
Technical field
The present invention relates to a kind of preparation method of bone peptide injection, belong to field of traditional Chinese.
Background technology
Bone peptide is the micromolecule polypeptide class material that extracts in the bones of limbs, has the adjusting bone metabolism, and stimulating osteoblast propagation promotes new bone formation, and regulates calcium, phosphorus metabolism, increases bone calcium deposition, prevents and treats the osteoporosis effect.Be used to promote union of fracture.
At present, the extraction process of some relevant bone peptides is disclosed, such as, patent documentation 200410013508.1, denomination of invention Bone Peptide for injection and its prepration technology, the polypeptides matter that bone extract system extracts from mammiferous bone, the molecular weight of described polypeptides matter is 3000-10000, described polypeptide is 1-100 with the content ratio of described excipient: 0.01, and pH value is 3.5-9.0, ninhydrin reaction is positive.This product is used for the treatment of hypertrophy joint disease and rheumatism, rheumatoid arthritis etc., and can promote union of fracture.
Patent documentation 200510076912.8, denomination of invention bone peptide injection and preparation method thereof, its preparation method is as follows: 1). and mammalian bone is boiled with saline hot pressing carry one or many, centrifugal filtration, merge leach cooking liquid, placed at low temperatures 1～40 hour, and, collected filtrate for later use the warm back centrifugal filtration of extracting solution; 2). with adding ethanol behind the filtrate vacuum concentration, staticly settle, sucking-off upper strata alcohol liquid, standardize solution reclaims ethanol, gets the water extract; 3). the water extract is added the equal-volume distilled water, and successively by acidulous cation resin post, weak anion resin post, pearl chitosan post and chitin modified activated-charcoal column, the roguing purification gets pure rare medicinal liquid; 4). after pure rare medicinal liquid concentrated, the microporous filter membrane that pressurizeed, with filtrate fill, sealing by fusing, pressure sterilizing, or with the gained medicinal liquid by lyophilization, obtain lyophilized injectable powder.
Patent documentation 200610150890.X, denomination of invention injection bone peptide freeze-drying agent and preparation method thereof, it comprises: (1), get healthy FF mammiferous bones of limbs and weigh, clean three times with purified water after, put on the hydraulic press and crush.With the bones of limbs of crushing, to put in the jacketed pan, 1: 1～5 adding 5%NaOH solution of press raw material weight heat 30～55 ℃ of hydrolysis and get supernatant after 12～48 hours; (2), supernatant puts in the jacketed pan with HCl adjust pH 3.0～6.0, is heated to 70～100 ℃ of 15～40min, cools to 30～55 ℃, leave standstill after 12～48 hours and filter with filter cloth.
Patent documentation 200510051475.4, a kind of bone peptide extract of denomination of invention, Its Preparation Method And Use, it extracts the mammal bones of limbs through hot pressing, steps such as cold preservation degrease, adjusting pH value precipitation, heating, centrifugal filtration, ultrafiltration make the bones of limbs extract.
Present most technology only adopts acid, alkali to precipitate the technology of acidic protein and basic protein respectively, its precision requirement to pH value is very high, otherwise the acid that adds, the amount of alkali more or less all can cause acidity or basic protein to remove unclean even can cause other impurity, influence product quality.
Summary of the invention
The preparation method that the purpose of this invention is to provide a kind of bone peptide injection, this technology can more effectively be removed impurity such as macro-molecular protein, guarantees the high-purity of product.
In order to realize the object of the invention, the preparation method of bone peptide injection of the present invention comprises the steps:
1) with pig or cattle limbs bone, clean, smash, add the purified water of 1～4 times of weight, 105～120 ℃ of high pressure extract at least 2 times, each 1～3 hour, merge extractive liquid, filtered, and the upper strata oils and fats is removed in cold preservation, and adjust pH 1.0～4.0 boils, cold preservation;
2) cross the leaching supernatant, be evaporated to 2.5～2.8g (bones of limbs)/ml, add ethanol and make and contain pure volume and reach 60～80%, leave standstill, filtered and recycled ethanol is to there not being the alcohol flavor; With the rare 1～2g/ml that is assigned to of water for injection, adjust pH 6.0～8.0; Filter sterilization; Freezing, rearmounted shady and cool lucifuge place of negative catalysis or room temperature are placed; Filter adjust pH 6.8～7.2; Decolouring, adjust pH 6.8～7.2, sterilization is refrigerated to icingly, takes out negative catalysis;
3) be diluted to every 1ml with the medicinal liquid of water for injection after with negative catalysis and contain polypeptide 5.0～15.0mg, coarse filtration is transferred pH6.8～7.5, fine straining, bone peptide injection.
Wherein, preferably, preparation method of the present invention comprises the steps:
1) with pig, cattle limbs bone, clean, be broken into the fritter of 5～10cm, add the purified water of 2～3 times of weight, 110～120 ℃, 0.08～0.1Mpa pressure extract 2 times down, be respectively 2～3 hours and 1～2 hour, merge extractive liquid, filters, in 0～5 ℃ of cold preservation 8～36 hours, remove the upper strata oils and fats, adjust pH 2.0～3.0 boiled 30～60 minutes, cold preservation 8～24 hours;
2) leaching supernatant is evaporated to 2.5～2.8g (bones of limbs)/ml at 70～75 ℃, treats that temperature is reduced to below 30 ℃ to add ethanol and make and contain pure volume and reach 70～80%, leaves standstill 8～24 hours after-filtration to clarification, reclaims ethanol to there not being the alcohol flavor; With the rare 1g/ml that is assigned to of water for injection, adjust pH 6.7～7.3; Filter paper filtering, 0.22 μ m membrane filtration, 6000～10000 molecular weight ultrafilter ultrafiltration were sterilized 40 minutes for 115 ℃; Be refrigerated to icingly, rearmounted shady and cool lucifuge place of negative catalysis or room temperature were placed 5～20 days; Again through 0.2 μ m membrane filtration, with 6000～10000 molecular weight ultrafilter ultrafiltration, adjust pH 6.8～7.2; Add 0.2% (g/ml) active carbon, heated and boiled 15～30 minutes is cooled to 40～60 ℃, 0.2 μ m membrane filtration, and adjust pH 6.8～7.2,115 ℃ of sterilizations 40 minutes are refrigerated to icingly, take out negative catalysis;
3) be diluted to every 1ml with the medicinal liquid of water for injection after with negative catalysis and contain polypeptide 5.0～10.0mg, coarse filtration is transferred pH6.8～7.5, fine straining, bone peptide injection.
The present invention also can be directly with bone peptide injection through lyophilization, the bone peptide freeze-drying injectable powder.
Or add the injection water earlier with after the excipient dissolving, add activated carbon decolorizing again, filter aqueous solution; Aqueous solution is joined in the described bone peptide injection, be adjusted to every 1ml and contain polypeptide 5.0～15.0mg, excipient 100～200mg, 0.45 μ m filter membrane coarse filtration is transferred pH6.8～7.5,0.2 μ m microporous filter membrane fine straining, and lyophilization gets the bone peptide freeze-drying injectable powder.
Described excipient is mannitol, lactose or glucosan etc.
The present invention adjusts pH and can adopt acid commonly used or alkali to carry out, such as hydrochloric acid or sodium hydroxide etc.
Described lyophilization can adopt this area technology, equipment commonly used to finish.Such as, vacuum lyophilization, technical process is several steps of pre-freeze, insulation, sublimation drying and finish-drying, finishes on the intravital shelving of drying baker.
The bone peptide injection that preparation technology of the present invention obtains, by the bones of limbs of fresh or refrigerated pig, cattle through high pressure extract, defat, acid treatment, precipitate with ethanol, alkali treatment, ultrafiltration forms.Adopt acid, alkali to remove acidic protein and basic protein in the bone respectively, also adopt precipitate with ethanol simultaneously, can remove impurity such as macro-molecular protein effectively, it is few to guarantee that bone peptide freezes injection impurity, the purity height.
The specific embodiment
Following examples are used to illustrate the present invention, but are not used for limiting the scope of the invention.
Embodiment 1
1. bone peptide solution extraction process
With fresh pig limbs bone, reject residual meat, clean, be broken into the fritter of 10cm.Add 2 times of amount purified water, 120 ℃, 0.1Mpa pressure extract 2 times down, be respectively 2 hours and 1 hour, and merge extractive liquid,, filtration was in 5 ℃ of cold preservations 24 hours.Remove the upper strata oils and fats,, boiled cold preservation 12 hours 40 minutes with 10% (volume, as follows) hydrochloric acid adjust pH 2.6.The leaching supernatant is evaporated to 2.8g (bones of limbs)/ml at 75 ℃, treats that temperature is reduced to below 30 ℃ to add ethanol and make and contain the alcohol amount and reach 70% (volume, as follows), leaves standstill 12 hours after-filtration to clarification, reclaims ethanol to there not being the alcohol flavor.With the rare 1g/ml that is assigned to of water for injection, 40%NaOH solution adjust pH 7.3.Filter paper filtering, 0.22 μ m membrane filtration, the ultrafiltration of 6000 molecular weight volume membrane type ultrafilter, fill was sterilized 40 minutes for 115 ℃.Be refrigerated to icingly, take out the rearmounted room temperature of negative catalysis and place a week.Pour out medicinal liquid, 0.2 μ m membrane filtration, adjust pH 6.8, with the ultrafiltration of 6000 molecular weight volume membrane type ultrafilter, the medicinal liquid after the collection ultrafiltration stirs 20% (volume, as follows) sodium hydroxide solution adjust pH 7.2.Add 0.2% (g/ml) active carbon, heated and boiled 15 minutes is cooled to 50 ℃, 0.2 μ m membrane filtration, and adjust pH 7.2, fill, 115 ℃ of sterilizations 40 minutes are refrigerated to icingly, take out negative catalysis.
2. injection bone peptide preparation technology
Claim mannitol, add the injection water and make its dissolving, add 0.3% (g/ml) medicinal charcoal again and stirred 15 minutes, filter carbon removal and get mannitol solution; Get the bone peptide frozen soln, room temperature is melted, and adds the mannitol solution for preparing, and adds the injection water and is adjusted to every 1ml and contains polypeptide 5mg, mannitol 100mg with 0.45 μ m filter membrane prefiltration, transfers pH7.2 with filtrate, through 0.2 μ m microporous filter membrane aseptic filtration, fill, lyophilization, promptly.
Embodiment 2
1. bone peptide solution extraction process
With refrigerated pig limbs bone, reject residual meat, clean, be broken into the fritter of 8cm.Add 2 times of amount purified water, 110 ℃, 0.08Mpa pressure extract 3 times down, are respectively 3 hours, 2.5 hours and 1.5 hours, and merge extractive liquid, filters, in 0 ℃ of cold preservation 12 hours.Remove the upper strata oils and fats,, boiled 30 minutes cold preservation 8 hours with 10% hydrochloric acid adjust pH 2.0.The leaching supernatant is evaporated to 2.5g (bones of limbs)/ml at 73 ℃, treats that temperature is reduced to below 30 ℃ to add ethanol and make and contain the alcohol amount and reach 80%, leaves standstill 8 hours after-filtration to clarification, reclaims ethanol to there not being the alcohol flavor.With the rare 2g/ml that is assigned to of water for injection, 40%NaOH solution adjust pH 6.0.Filter paper filtering, 0.22 μ m membrane filtration, the ultrafiltration of 8000 molecular weight volume membrane type ultrafilter, fill was sterilized 40 minutes for 115 ℃.Be refrigerated to icingly, take out the rearmounted shady and cool lucifuge of negative catalysis place and placed 10 days.Pour out medicinal liquid, 0.2 μ m membrane filtration, adjust pH 6.8, with the ultrafiltration of 8000 molecular weight volume membrane type ultrafilter, the medicinal liquid after the collection ultrafiltration stirs 20% sodium hydroxide solution adjust pH 7.0.Add 0.2% (g/ml) active carbon, heated and boiled 20 minutes is cooled to 60 ℃, 0.2 μ m membrane filtration, and adjust pH 7.0, fill, 115 ℃ of sterilizations 40 minutes are refrigerated to icingly, take out negative catalysis.
2. injection bone peptide preparation technology
With the bone peptide frozen soln, room temperature is melted, and adds injection again and is diluted with water to every 1ml and contains polypeptide 10mg, with 0.45 μ m filter membrane prefiltration, filtrate is transferred pH6.8, through 0.2 μ m microporous filter membrane aseptic filtration, and fill, lyophilization, promptly.
Embodiment 3
1. bone peptide solution extraction process
With fresh or refrigerated cattle limbs bone, reject residual meat, clean, be broken into the fritter of 7cm.Add 3 times of amount purified water, following 2 times of 112 ℃, 0.09Mpa pressure were respectively 2.5 hours and 2 hours, merge extractive liquid,, and filtration was in 0 ℃ of cold preservation 12 hours.Remove the upper strata oils and fats,, boiled 60 minutes cold preservation 20 hours with 10% hydrochloric acid adjust pH 2.6.The leaching supernatant is evaporated to 2.6g (bones of limbs)/ml at 75 ℃, treats that temperature is reduced to below 30 ℃ to add ethanol and make and contain the alcohol amount and reach 65%, leaves standstill 24 hours after-filtration to clarification, reclaims ethanol to there not being the alcohol flavor.With the rare 2g/ml that is assigned to of water for injection, 40%NaOH solution adjust pH 6.7.Filter paper filtering, 0.22 μ m membrane filtration, the ultrafiltration of 10000 molecular weight volume membrane type ultrafilter, fill was sterilized 40 minutes for 115 ℃.Be refrigerated to icingly, take out the rearmounted room temperature of negative catalysis and placed 15 days.Pour out medicinal liquid, 0.2 μ m membrane filtration, adjust pH 7.2, with the ultrafiltration of 10000 molecular weight volume membrane type ultrafilter, the medicinal liquid after the collection ultrafiltration stirs 20% sodium hydroxide solution adjust pH 7.2.Add 0.2% (g/ml) active carbon, heated and boiled 15 minutes is cooled to 40 ℃, 0.2 μ m membrane filtration, and adjust pH 7.2, fill, 115 ℃ of sterilizations 40 minutes are refrigerated to icingly, take out negative catalysis.
2. injection bone peptide preparation technology
Take by weighing lactose, add proper amount of water for injection and make its dissolving, add 0.3% (g/ml) medicinal charcoal again and stirred 15 minutes, filter carbon removal and get lactose solution; Get the bone peptide frozen soln, room temperature is melted, and adds the lactose solution for preparing, and adds the every 1ml of injection water again and contains polypeptide 5.5mg, lactose 150mg with 0.45 μ m filter membrane prefiltration, transfers pH7.5 with filtrate, through 0.2 μ m microporous filter membrane aseptic filtration, fill, lyophilization, promptly.
Embodiment 4
1. bone peptide solution extraction process
With fresh or refrigerated pig limbs bone, reject residual meat, clean, be broken into the fritter of 6cm.Add 3 times of amount purified water, high pressure extract is 3 times under 115 ℃, 0.1Mpa pressure, is respectively 2 hours, 1.5 hours and 1 hour, and merge extractive liquid, filters, in 5 ℃ of cold preservations 36 hours.Remove the upper strata oils and fats,, boiled 50 minutes cold preservation 16 hours with 10% hydrochloric acid adjust pH 3.5.The leaching supernatant is evaporated to 2.6g (bones of limbs)/ml at 70 ℃, treats that temperature is reduced to below 30 ℃ to add ethanol and make and contain the alcohol amount and reach 70%, leaves standstill 20 hours after-filtration to clarification, reclaims ethanol to there not being the alcohol flavor.With the rare 1g/ml that is assigned to of water for injection, 40%NaOH solution adjust pH 8.0.Filter paper filtering, 0.22 μ m membrane filtration, the ultrafiltration of 10000 molecular weight volume membrane type ultrafilter, fill was sterilized 40 minutes for 115 ℃.Be refrigerated to icingly, take out the rearmounted shady and cool lucifuge of negative catalysis place and placed 5 days.Pour out medicinal liquid, 0.2 μ m membrane filtration, adjust pH 7.0, with the ultrafiltration of 10000 molecular weight volume membrane type ultrafilter, the medicinal liquid after the collection ultrafiltration stirs 20% sodium hydroxide solution adjust pH 6.8.Add 0.2% (g/ml) active carbon, heated and boiled 30 minutes is cooled to 60 ℃, 0.2 μ m membrane filtration, and adjust pH 6.8, fill, 115 ℃ of sterilizations 40 minutes are refrigerated to icingly, take out negative catalysis.
2. injection bone peptide preparation technology
Get glucosan, add water and make its dissolving, add 0.3% (g/ml) medicinal charcoal again and stirred 15 minutes, filter carbon removal and get dextran solution; Get recipe quantity bone peptide frozen soln, room temperature is melted, and adds the dextran solution for preparing, and adds the every 1ml of injection water again and contains polypeptide 15mg, Dextran 200 mg with 0.45 μ m filter membrane prefiltration, transfers pH7.0 with filtrate, through 0.2 μ m microporous filter membrane aseptic filtration, fill, lyophilization, promptly.
Embodiment 5
1. bone peptide solution extraction process
With fresh or refrigerated cattle limbs bone, reject residual meat, clean, be broken into the fritter of 6cm.Add 3 times of amount purified water, high pressure extract is 3 times under 115 ℃, 0.08Mpa pressure, is respectively 2 hours, 1.5 hours and 1 hour, and merge extractive liquid, filters, in 5 ℃ of cold preservations 36 hours.Remove the upper strata oils and fats,, boiled 50 minutes cold preservation 16 hours with 10% hydrochloric acid adjust pH 3.5.The leaching supernatant is evaporated to 2.6g (bones of limbs)/ml at 70 ℃, treats that temperature is reduced to below 30 ℃ to add ethanol and make and contain the alcohol amount and reach 70%, leaves standstill 20 hours after-filtration to clarification, reclaims ethanol to there not being the alcohol flavor.With the rare 1g/ml that is assigned to of water for injection, 40%NaOH solution adjust pH 7.3.Filter paper filtering, 0.22 μ m membrane filtration, the ultrafiltration of 6000 molecular weight volume membrane type ultrafilter, fill was sterilized 40 minutes for 115 ℃.Be refrigerated to icingly, take out the rearmounted shady and cool lucifuge of negative catalysis place and placed 6 days.Pour out medicinal liquid, 0.2 μ m membrane filtration, adjust pH 7.2, with the ultrafiltration of 10000 molecular weight volume membrane type ultrafilter, the medicinal liquid after the collection ultrafiltration stirs 20% sodium hydroxide solution adjust pH 7.0.Add 0.2% (g/ml) active carbon, heated and boiled 30 minutes is cooled to 60 ℃, 0.2 μ m membrane filtration, and adjust pH 7.2, fill, 115 ℃ of sterilizations 40 minutes are refrigerated to icingly, take out negative catalysis.
2. bone peptide injection preparation technology
Be diluted to every 1ml with the medicinal liquid of water for injection after with negative catalysis and contain polypeptide 8mg, 0.2 μ m membrane filtration is transferred pH7.5, through 0.2 μ m microporous filter membrane aseptic filtration, bone peptide injection.
Experimental example 1
1) proteinic inspection: get bone peptide injection 1ml or 1 injection bone peptide and add water and make the solution that every 1ml contains the about 5mg of polypeptides matter, add 30% sulfosalicylic acid solution 1ml of new preparation, mixing was placed 5 minutes, did not all become turbid.
2) particulate matter inspection: get each 1 of the bone peptide preparation that lyophilized injectable powder that embodiment 1-3 method obtains and existing technology obtains, add the microgranule inspection with the dissolving of purifying waste water, do blank with coordinative solvent, check (an appendix IX of Chinese Pharmacopoeia version in 2005 R) in accordance with the law, every microgranule that contains more than the 10 μ m must not be crossed 6000, contains the above microgranule of 25 μ m and must not cross 600.Actual detected 3 batch samples the results are shown in Table 1.
Table 1
| The microgranule (individual/as to prop up) that 10 μ m are above | The microgranule (individual/as to prop up) that 25 μ m are above | ||
| Sample | 1 | 600 | 50 |
| 2 | 654 | 71 | |
| 3 | 623 | 65 | |
| Common process | 1 | 1355 | 153 |
| 2 | 1842 | 240 | |
| 3 | 1600 | 201 | |
3) clarity of solution and color: get injection bone peptide and add water and make the solution that contains the about 5mg of polypeptides matter among every 1ml, the solution clarification, color is shallower than yellow No. 2 standard color solutions.
4) undue toxicity: get injection bone peptide, add the chlorination sodium injection and make the solution that contains the about 5mg of polypeptides matter among every 1ml, check (" two appendix XIC of Chinese pharmacopoeia version in 2005), press the intravenous injection administration, up to specification. in accordance with the law
5) allergic experiment: get injection bone peptide, add sterilized water for injection and make and contain the solution of the about 5mg of polypeptides matter among every 1ml or directly get bone peptide injection as need testing solution.Get body weight and be 6 of the healthy guinea pigs of 250～350g, continuous 3 times, every other day lumbar injection need testing solution 0.5ml.After injecting for two weeks for the third time,, inject in back 15 minutes, anaphylaxis all do not occur again from intravenous injection this product 1ml.
Conclusion: by the bone peptide preparation of the present invention's preparation, impurity is few, purity height, application safety.
Claims (5)
1. the preparation method of a bone peptide injection is characterized in that, comprises the steps:
1) with pig or cattle limbs bone, clean, smash, add the purified water of 1～4 times of weight, 105～120 ℃ of high pressure extract at least 2 times, each 1～3 hour, merge extractive liquid, filtered, and the upper strata oils and fats is removed in cold preservation, and adjust pH 1.0～4.0 boils, cold preservation;
2) cross the leaching supernatant, be evaporated to 2.5～2.8g (bones of limbs)/ml, add ethanol and make and contain pure volume and reach 60～80%, leave standstill, filtered and recycled ethanol is to there not being the alcohol flavor; With the rare 1～2g/ml that is assigned to of water for injection, adjust pH 6.0～8.0; Filter sterilization; Freezing, rearmounted shady and cool lucifuge place of negative catalysis or room temperature are placed; Filter adjust pH 6.8～7.2; Decolouring, adjust pH 6.8～7.2, sterilization is refrigerated to icingly, takes out negative catalysis;
3) be diluted to every 1ml with the medicinal liquid of water for injection after with negative catalysis and contain polypeptide 5.0～15.0mg, coarse filtration is transferred pH6.8～7.5, fine straining, bone peptide injection.
2. the preparation method of bone peptide injection according to claim 1 is characterized in that, comprises the steps:
1) with pig, cattle limbs bone, clean, be broken into the fritter of 5～10cm, add the purified water of 2～3 times of weight, 110～120 ℃, 0.08～0.1Mpa pressure extract 2 times down, be respectively 2～3 hours and 1～2 hour, merge extractive liquid, filters, in 0～5 ℃ of cold preservation 8～36 hours, remove the upper strata oils and fats, adjust pH 2.0～3.0 boiled 30～60 minutes, cold preservation 8～24 hours;
2) leaching supernatant is evaporated to 2.5～2.8g (bones of limbs)/ml at 70～75 ℃, treats that temperature is reduced to below 30 ℃ to add ethanol and make and contain pure volume and reach 70～80%, leaves standstill 8～24 hours after-filtration to clarification, reclaims ethanol to there not being the alcohol flavor; With the rare 1g/ml that is assigned to of water for injection, adjust pH 6.7～7.3; Filter paper filtering, 0.22 μ m membrane filtration, 6000～10000 molecular weight ultrafilter ultrafiltration were sterilized 40 minutes for 115 ℃; Be refrigerated to icingly, rearmounted shady and cool lucifuge place of negative catalysis or room temperature were placed 5～20 days; Again through 0.2 μ m membrane filtration, with 6000～10000 molecular weight ultrafilter ultrafiltration, adjust pH 6.8～7.2; Add 0.2% (g/ml) active carbon, heated and boiled 15～30 minutes is cooled to 40～60 ℃, 0.2 μ m membrane filtration, and adjust pH 6.8～7.2,115 ℃ of sterilizations 40 minutes are refrigerated to icingly, take out negative catalysis;
3) be diluted to every 1ml with the medicinal liquid of water for injection after with negative catalysis and contain polypeptide 5.0～10.0mg, coarse filtration is transferred pH6.8～7.5, fine straining, bone peptide injection.
3. the preparation method of bone peptide injection according to claim 1 and 2 is characterized in that, also comprises step 4): described bone peptide injection gets the bone peptide freeze-drying injectable powder through lyophilization.
4. the preparation method of bone peptide injection according to claim 1 and 2 is characterized in that, also comprises step 4): add the injection water earlier with after the excipient dissolving, add activated carbon decolorizing again, filter aqueous solution; Aqueous solution is joined in the described bone peptide injection, be adjusted to every 1ml and contain polypeptide 5.0～15.0mg, excipient 100～200mg, 0.45 μ m filter membrane coarse filtration is transferred pH6.8～7.5,0.2 μ m microporous filter membrane fine straining, and lyophilization gets the bone peptide freeze-drying injectable powder.
5. the preparation method of bone peptide injection according to claim 4 is characterized in that, described excipient is mannitol, lactose or glucosan.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB2007100996296A CN100457178C (en) | 2007-05-25 | 2007-05-25 | Process for preparing bone peptide injection |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB2007100996296A CN100457178C (en) | 2007-05-25 | 2007-05-25 | Process for preparing bone peptide injection |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN101062403A true CN101062403A (en) | 2007-10-31 |
| CN100457178C CN100457178C (en) | 2009-02-04 |
Family
ID=38963820
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CNB2007100996296A Active CN100457178C (en) | 2007-05-25 | 2007-05-25 | Process for preparing bone peptide injection |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN100457178C (en) |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101933944A (en) * | 2010-09-26 | 2011-01-05 | 武汉华龙生物制药有限公司 | Method for preparing bone peptide injection |
| CN104522793A (en) * | 2014-12-06 | 2015-04-22 | 黑龙江众生生物工程有限公司 | A preparation method of a pure biological agent beverage for increasing the bone density |
| CN104974219A (en) * | 2015-07-14 | 2015-10-14 | 河北智同生物制药有限公司 | Convenient ossotide alcohol precipitation tank and application method thereof |
| CN110898002A (en) * | 2019-12-06 | 2020-03-24 | 湖北威仕生物药业股份有限公司 | Bone peptide injection and preparation method and application thereof |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1287851C (en) * | 2003-02-26 | 2006-12-06 | 江卫世 | Ossotide sodium chloride injection and its preparing process |
| CN1318085C (en) * | 2005-06-09 | 2007-05-30 | 赵红梅 | Ossotide injection and preparation method thereof |
| CN100569282C (en) * | 2006-10-13 | 2009-12-16 | 俞嘉林 | Injection bone peptide freeze-drying agent and preparation method thereof |
-
2007
- 2007-05-25 CN CNB2007100996296A patent/CN100457178C/en active Active
Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101933944A (en) * | 2010-09-26 | 2011-01-05 | 武汉华龙生物制药有限公司 | Method for preparing bone peptide injection |
| CN101933944B (en) * | 2010-09-26 | 2012-05-23 | 武汉华龙生物制药有限公司 | Method for preparing bone peptide injection |
| CN104522793A (en) * | 2014-12-06 | 2015-04-22 | 黑龙江众生生物工程有限公司 | A preparation method of a pure biological agent beverage for increasing the bone density |
| CN104974219A (en) * | 2015-07-14 | 2015-10-14 | 河北智同生物制药有限公司 | Convenient ossotide alcohol precipitation tank and application method thereof |
| CN110898002A (en) * | 2019-12-06 | 2020-03-24 | 湖北威仕生物药业股份有限公司 | Bone peptide injection and preparation method and application thereof |
| CN110898002B (en) * | 2019-12-06 | 2022-05-10 | 湖北威仕生物药业股份有限公司 | Bone peptide injection and preparation method and application thereof |
Also Published As
| Publication number | Publication date |
|---|---|
| CN100457178C (en) | 2009-02-04 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN101475626B (en) | Method for extracting transfer factor from pig spleen | |
| CN101628025B (en) | Pharmaceutical composition containing deer bone extractive and melon seed extract | |
| CN1857711A (en) | Brain protein hydrolysate and production process of its freeze dried preparation | |
| CN101057864A (en) | Technology for preparing anti influenza virus transfer factors | |
| CN100457178C (en) | Process for preparing bone peptide injection | |
| CN1290862C (en) | Spleen polypeptide extract, its preparing process and use | |
| CN1228082C (en) | Method for preparing pharmaceutics of hydrolysate of brain protein | |
| CN102908363B (en) | Deproteinized calf blood extract and preparation process thereof | |
| CN101103999A (en) | Bone peptide injection preparation technology | |
| KR20180028229A (en) | The Method of High-yield and High-purity Manufacturing of Allo-collagen Composition Extracted From Human origin | |
| CN102167726A (en) | Method for separating and extracting active polypeptide and immune ribonucleic acid by utilizing blood and spleen of animal | |
| CN1742778A (en) | Cervus and cucumis polypeptide injection composition and preparing method | |
| EP0395757B1 (en) | Process for extracting physiologically active substance from pine seed shells and antiinfectant prepared mainly from the extract | |
| CN1857300A (en) | Freeze dried ginseng polysaccharide powder for injection and its preparing process | |
| CN1939342A (en) | Injection bone peptide freeze-drying preparation and its making method | |
| CN1698655A (en) | Ossotide injection and preparation method thereof | |
| CN104096214A (en) | Cerebroprotein hydrolysate freeze-dried powder injection and preparation method thereof | |
| KR101407611B1 (en) | Dioscoreae Rhizoma comprising the manufacture of a medicament for the treatment of facial nerve paralysis, and the extract beongbeop | |
| CN103041366B (en) | Bone peptide composition and preparation method thereof | |
| CN1038512C (en) | Medicine for improving growth of liver cell and its method for production | |
| CN1939343A (en) | Bone-peptide sodium chloride injection and its making method | |
| CN101049339A (en) | Method for preparing injection of astragalus | |
| CN1823606A (en) | Edible watural silk protein powder and preparation method of natural silk extract | |
| CN100391474C (en) | Injection medicine for treating platelet abatement | |
| CN101732697B (en) | Compound frozen ossotide preparation |
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 | ||
| C56 | Change in the name or address of the patentee |
Owner name: HEILONGJIANG ZHENBAODAO PHARMACEUTICAL CO., LTD. Free format text: FORMER NAME: ZHENBAODAO PHARMACEUTICAL CO., LTD., HELONGJIANG |
|
| CP01 | Change in the name or title of a patent holder |
Address after: 158400 Hulin Red Star Street, Heilongjiang, No. 72 Patentee after: Heilongjiang ZBD Pharmaceutical Co., Ltd. Address before: 158400 Hulin Red Star Street, Heilongjiang, No. 72 Patentee before: Helongjiang Zhenbaodao Pharmaceutical Co., Ltd. |