CN1415378A - Injection of freeze-dried powder of growth hormone release inhibiting hormone and its preparation method - Google Patents
Injection of freeze-dried powder of growth hormone release inhibiting hormone and its preparation method Download PDFInfo
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- CN1415378A CN1415378A CN 02138477 CN02138477A CN1415378A CN 1415378 A CN1415378 A CN 1415378A CN 02138477 CN02138477 CN 02138477 CN 02138477 A CN02138477 A CN 02138477A CN 1415378 A CN1415378 A CN 1415378A
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- freeze
- somatostatin
- dried powder
- injection
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- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Abstract
A freeze dried somatostatin powder injection is prepared through dissolving the excipient in the water for injection, adding activated carbon, stirring at 20-60 deg.c for 20-80 min, dissolving somatostation in it adding pH regulator to regulate the pH value of solution to 4-6, adding water for injection, filtering by membrane, loading in glass bottles, freeze drying and sealing.
Description
Technical field
The present invention relates to a kind of somatostatin freeze-dried powder and preparation technology thereof.
Background technology
Somatostatin is the ring tetradecapeptide that comes out from the hypothalamus separation and purification in 1973, be present in human central nervous system and peripheral organs (as stomach, intestinal, pancreas, skin etc.), its Cmax sees hypothalamus, but contains the total amount maximum with digestive tract, and wherein gastric antrum and islets of langerhans intensive amount are maximum.It is to act on the most a kind of hypothalamus neurohormone, can suppress secretion and other multiple endocrine function of multiple gastrointestinal hormone.Somatostatin is one of hormone medicine of the tool effect of the clinical practice nineties, and it is hemorrhage to be used for the treatment of acute esophageal varicosis, and digestive tract ulcer is hemorrhage, acute pancreatitis.Its clinical usage is generally somatostatin 250 μ g intravenous injections, then with the per hour speed intravenous drip of 25 μ g.After the stopped bleeding to be confirmed, continue again to use to get final product drug withdrawal in 24-48 hour.The spontaneous growth chalone be difficult to be realized industrialized great production, and somatostatin has been realized synthetic now, can produce greatly, and the chemical constitution of synthetically grown chalone and spontaneous growth chalone and pharmacological action aspect is identical.Existing somatostatin generally is used for clinical with the form of freeze-dried powder, but the producting process difficulty of existing somatostatin freeze-dried powder is bigger, and cost is higher, and product colour and molding are all relatively poor.
Summary of the invention
The technical problem to be solved in the present invention is exactly that the prior art producting process difficulty is bigger, and cost is higher, the problem that product colour and molding are all relatively poor.
Somatostatin freeze-dried powder of the present invention is made by following proportioning by following component:
Ratio of component one:
Somatostatin 250mg
Excipient 5000-20000mg
PH regulator agent 0-100ml
Water for injection 600ml
Ratio of component two:
Somatostatin 3000mg
Excipient 5000-20000mg
PH regulator agent 0-100ml
Water for injection 600ml
In above-mentioned technology, the present invention mainly adopts in mannitol, the lactose one or both as excipient, by screening different proportion excipient to reach ideal effect.The present invention mainly adopt in hydrochloric acid, phosphoric acid, citric acid, glacial acetic acid, the acetic acid etc. any one or more than one as the pH regulator agent, to reach the required requirement of human injection.
The production technology of the present invention's somatostatin freeze-dried powder comprises the steps:
(1) excipient is placed the beaker of sterilizing, add water for injection, after stirring and the dissolving, add the 0.1-0.3% needle-use activated carbon, 20-60 ℃ was stirred 20-80 minute down;
(2) somatostatin is added the 0.6 μ m filter membrane of using through sterilization and take off in the charcoal, fully stir and make dissolving,, add the injection water to the 600ml scale, with 0.22 μ m membrane filtration degerming with pH regulator agent regulator solution pH value to 4.0～6.0;
(3) loading amount by every bottle of 0.6ml is sub-packed in the glass glass tube vial, sends into the freezer dryer lyophilizing, adds a cover, and labels promptly.
Whole process of preparation is carried out on clean bench, and the freeze-drying curve of freezing dry process as follows
Operation heating rate time (h) temperature (℃)
1 pre-freeze 1-5 room temperature is chilled to-30 ℃--and 50 ℃
0.5-3-30 ℃ of 2 insulation--50 ℃
0.5-30 ℃ of 3 evacuation--50 ℃
4 intensification 5-10 ℃/hour 2.5-9 are warming up to-5 ℃
5 intensification 2-6-5 ℃ are warming up to 0 ℃
6 intensification 2-6 are warming up to 10 ℃ for 0 ℃
7 intensification 2-5 are warming up to 25 ℃ for 10 ℃
25 ℃ of 8 insulation 2-5
Prescription of the present invention and production technology are simple, are convenient to operation, are fit to large-scale production, obviously improve molded appearance, and the lyophilized powder agllutination is real full, be translucent.Can supply intravenous drip administration, the toxic and side effects of avoiding intravenous injection to cause.
The specific embodiment
The specific embodiment one:
Whole process of preparation is carried out on clean bench.
Take by weighing 15000mg mannitol, place the beaker of sterilizing, add 200ml water for injection, after stirring and the dissolving, add 0.1% needle-use activated carbon, 40 ℃ were stirred 30 minutes down, used 0.6 μ m filter membrane through sterilization to take off charcoal, the somatostatin that takes by weighing 250mg adds wherein, fully stir and make dissolving,, add the injection water to the 600ml scale with pH regulator agent regulator solution pH value to 5.0, with 0.22 μ m membrane filtration degerming, loading amount by every bottle of 0.6ml is sub-packed in the glass glass tube vial, altogether 1000 bottles, send into freezer dryer lyophilizing (freeze-drying curve is as follows), add a cover, label promptly.
Freeze-drying curve:
Operation heating rate time (h) temperature (℃)
1 pre-freeze, 3 room temperatures are chilled to-40 ℃
1-35 ℃ of 2 insulation
0.5-35 ℃ of 3 evacuation
4 heat up is warming up to-5 ℃ for 5 ℃/hour 6
5 heat up 4-5 ℃ is warming up to 0 ℃
6 heat up 30 ℃ is warming up to 10 ℃
7 heat up 3 10 ℃ is warming up to 25 ℃
2 25 ℃ of 8 insulations
The specific embodiment two:
Whole process of preparation is carried out on clean bench.
Take by weighing the 10000mg lactose, place the beaker of sterilizing, add 200ml water for injection, after stirring and the dissolving, add 0.2% needle-use activated carbon, 50 ℃ were stirred 20 minutes down, used 0.6 μ m filter membrane through sterilization to take off charcoal, taking by weighing the 3000mg somatostatin adds wherein, fully stir and make dissolving,, add the injection water to the 600ml scale with glacial acetic acid regulator solution pH value to 5.5, with 0.22 μ m membrane filtration degerming, loading amount by every bottle of 0.6ml is sub-packed in the glass glass tube vial, altogether 1000 bottles, send into freezer dryer lyophilizing (freeze-drying curve is as follows), add a cover, label promptly.
Freeze-drying curve:
Operation heating rate time (h) temperature (℃)
1 pre-freeze, 1.5 room temperatures are chilled to-40 ℃
0.5-40 ℃ of 2 insulation
0.5-40 ℃ of 3 evacuation
4 heat up is warming up to-5 ℃ for 7 ℃/hour 5
5 heat up 5-5 ℃ is warming up to 0 ℃
6 heat up 40 ℃ is warming up to 10 ℃
7 heat up 3 10 ℃ is warming up to 25 ℃
3 25 ℃ of 8 insulations
According to the relevant form and the requirement of Pharmacopoeia of the People's Republic of China version in 2000, character, discriminating, inspection and the assay etc. of somatostatin freeze-dried powder are studied, all meet the requirements.
The requirement that has according to Pharmacopoeia of the People's Republic of China version in 2000, stability to this product is studied, 60 ℃, high light (4500Lx) irradiation, high humidity RH75%, high humidity RH92.5%, accelerated test (the simulation listing is packaged under 40 ℃ of conditions and places), the chamber projects such as investigation that surely keep sample have been investigated, catabolite, content etc. have been measured, the somatostatin freeze-dried powder is stable in accelerated test and room temperature keep sample test, the character no change, catabolite does not have significant change.
Claims (6)
1, a kind of somatostatin freeze-dried powder is characterized in that it is made by following proportioning by following component:
Somatostatin 250mg
Excipient 5000-20000mg
PH regulator agent 0-100ml
Water for injection is to 600ml
2, a kind of somatostatin freeze-dried powder is characterized in that it is made by following proportioning by following component:
Somatostatin 3000mg
Excipient 5000-20000mg
PH regulator agent 0-100ml
Water for injection is to 600ml
3, somatostatin freeze-dried powder according to claim 1 and 2 is characterized in that described excipient is one or both in mannitol, the lactose.
4, somatostatin freeze-dried powder according to claim 1 and 2, it is characterized in that described pH regulator agent be in hydrochloric acid, phosphoric acid, citric acid, glacial acetic acid, the acetic acid any one or more than one.
5, a kind of preparation technology who is used for the described somatostatin freeze-dried powder of any claim of production claim 1-4 is characterized in that comprising the steps:
(1) excipient is placed the beaker of sterilizing, add water for injection, after stirring and the dissolving, add the 0.1-0.3% needle-use activated carbon, 20-60 ℃ was stirred 20-80 minute down;
(2) somatostatin is added the 0.6 μ m filter membrane of using through sterilization and take off in the charcoal, fully stir and make dissolving,, add the injection water to the 600ml scale, with 0.22 μ m membrane filtration degerming with pH regulator agent regulator solution pH value to 4.0～6.0;
(3) loading amount by every bottle of 0.6ml is sub-packed in the glass glass tube vial, sends into the freezer dryer lyophilizing, adds a cover, and labels promptly.
6, the preparation technology of somatostatin freeze-dried powder according to claim 5, the freeze-drying curve that it is characterized in that freezing dry process as follows:
Operation heating rate time (h) temperature (℃)
(1) pre-freeze 1-5 room temperature is chilled to-30 ℃--and 50 ℃
(2) insulation is 0.5-3-30 ℃--and 50 ℃
(3) evacuation is 0.5-30 ℃--and 50 ℃
(4) intensification 5-10 ℃ of/hour 2.5-9 is warming up to-5 ℃
(5) intensification 2-6-5 ℃ is warming up to 0 ℃
(6) intensification 2-6 is warming up to 10 ℃ for 0 ℃
(7) intensification 2-5 is warming up to 25 ℃ for 10 ℃
(8) insulation 2-5 is 25 ℃
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 02138477 CN1415378A (en) | 2002-10-22 | 2002-10-22 | Injection of freeze-dried powder of growth hormone release inhibiting hormone and its preparation method |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 02138477 CN1415378A (en) | 2002-10-22 | 2002-10-22 | Injection of freeze-dried powder of growth hormone release inhibiting hormone and its preparation method |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN1415378A true CN1415378A (en) | 2003-05-07 |
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| CN 02138477 Pending CN1415378A (en) | 2002-10-22 | 2002-10-22 | Injection of freeze-dried powder of growth hormone release inhibiting hormone and its preparation method |
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Cited By (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101700233B (en) * | 2009-12-04 | 2011-07-20 | 马鞍山丰原制药有限公司 | Method for preparing gonadorelin freeze-dried powder injection |
| CN101637455B (en) * | 2008-07-30 | 2011-12-07 | 南京长澳医药科技有限公司 | Eptifibatide powder injection |
| CN102711728A (en) * | 2010-01-13 | 2012-10-03 | 益普生制药股份有限公司 | Process for the preparation of pharmaceutical compositions for the sustained release of somatostatin analogs |
| CN103222963A (en) * | 2013-05-24 | 2013-07-31 | 成都天台山制药有限公司 | Somatostatin freeze-dried powder injection |
| CN103417499A (en) * | 2013-07-25 | 2013-12-04 | 武汉华龙生物制药有限公司 | Preparation method of somatostatin freeze-dried powder injection |
| CN109044980A (en) * | 2018-10-18 | 2018-12-21 | 成都天台山制药有限公司 | Growth hormone release inhibiting hormone freeze drying powder injection pharmaceutical composition and preparation method thereof |
| US10543249B2 (en) | 2013-07-09 | 2020-01-28 | Ipsen Pharma S.A.S. | Pharmaceutical composition for a sustained release of lanreotide |
| CN115252546A (en) * | 2022-09-06 | 2022-11-01 | 成都天台山制药有限公司 | Somatostatin composition for injection and preparation method thereof |
-
2002
- 2002-10-22 CN CN 02138477 patent/CN1415378A/en active Pending
Cited By (19)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101637455B (en) * | 2008-07-30 | 2011-12-07 | 南京长澳医药科技有限公司 | Eptifibatide powder injection |
| CN101700233B (en) * | 2009-12-04 | 2011-07-20 | 马鞍山丰原制药有限公司 | Method for preparing gonadorelin freeze-dried powder injection |
| CN102711728B (en) * | 2010-01-13 | 2016-01-20 | 益普生制药股份有限公司 | For delaying the preparation method of the pharmaceutical composition discharging somatostatin analogue |
| KR101915820B1 (en) * | 2010-01-13 | 2018-11-06 | 입센 파마 에스.에이.에스 | Process for the preparation of pharmaceutical compositions for the sustained release of somatostatin analogs |
| US20130079282A1 (en) * | 2010-01-13 | 2013-03-28 | Ipsen Pharma S.A.S. | Process for the preparation of pharmaceutical compositions for the sustained release of somatostatin analogs |
| US10206968B2 (en) | 2010-01-13 | 2019-02-19 | Ipsen Pharma S.A.S. | Process for the preparation of pharmaceutical compositions for the sustained release of somatostatin analogs |
| CN105456206B (en) * | 2010-01-13 | 2018-12-14 | 益普生制药股份有限公司 | For delaying to discharge the preparation method of the pharmaceutical composition of SMS 201-995 |
| KR20120125576A (en) * | 2010-01-13 | 2012-11-15 | 입센 파마 에스.에이.에스 | Process for the preparation of pharmaceutical compositions for the sustained release of somatostatin analogs |
| CN102711728A (en) * | 2010-01-13 | 2012-10-03 | 益普生制药股份有限公司 | Process for the preparation of pharmaceutical compositions for the sustained release of somatostatin analogs |
| CN105456206A (en) * | 2010-01-13 | 2016-04-06 | 益普生制药股份有限公司 | Process for the preparation of pharmaceutical compositions for the sustained release of somatostatin analogs |
| US9352012B2 (en) * | 2010-01-13 | 2016-05-31 | Ipsen Pharma S.A.S. | Process for the preparation of pharmaceutical compositions for the sustained release of somatostatin analogs |
| CN103222963B (en) * | 2013-05-24 | 2014-07-09 | 成都天台山制药有限公司 | Somatostatin freeze-dried powder injection |
| CN103222963A (en) * | 2013-05-24 | 2013-07-31 | 成都天台山制药有限公司 | Somatostatin freeze-dried powder injection |
| US10543249B2 (en) | 2013-07-09 | 2020-01-28 | Ipsen Pharma S.A.S. | Pharmaceutical composition for a sustained release of lanreotide |
| CN103417499A (en) * | 2013-07-25 | 2013-12-04 | 武汉华龙生物制药有限公司 | Preparation method of somatostatin freeze-dried powder injection |
| CN109044980A (en) * | 2018-10-18 | 2018-12-21 | 成都天台山制药有限公司 | Growth hormone release inhibiting hormone freeze drying powder injection pharmaceutical composition and preparation method thereof |
| CN109044980B (en) * | 2018-10-18 | 2020-11-24 | 成都天台山制药有限公司 | Somatostatin freeze-dried powder injection pharmaceutical composition and preparation method thereof |
| CN115252546A (en) * | 2022-09-06 | 2022-11-01 | 成都天台山制药有限公司 | Somatostatin composition for injection and preparation method thereof |
| CN115252546B (en) * | 2022-09-06 | 2024-04-30 | 成都天台山制药股份有限公司 | Somatostatin composition for injection and preparation method thereof |
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