CN106619498B - A kind of production method of asarone sodium chloride injection - Google Patents
A kind of production method of asarone sodium chloride injection Download PDFInfo
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- CN106619498B CN106619498B CN201611178976.3A CN201611178976A CN106619498B CN 106619498 B CN106619498 B CN 106619498B CN 201611178976 A CN201611178976 A CN 201611178976A CN 106619498 B CN106619498 B CN 106619498B
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- nitrogen
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- asarone
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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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/075—Ethers or acetals
- A61K31/085—Ethers or acetals having an ether linkage to aromatic ring nuclear carbon
- A61K31/09—Ethers or acetals having an ether linkage to aromatic ring nuclear carbon having two or more such linkages
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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
- A61K47/02—Inorganic compounds
-
- 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
- A61K47/26—Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
-
- 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
Abstract
The present invention relates to a kind of improved methods of asarone sodium chloride injection production technology; the present invention is by improving deoxygenation nitrogen charging mode; it is filling to use nitrogen filled protection medical fluid three times; nitrogen charging on liquid level is used after having medical fluid in dilute preparation; foam volume is reduced, nitrogen protection medical fluid is preferably utilized, stablizes asarone content; it reduces visible foreign matters to generate, improves yield rate.After method application of the invention, beneficial effect is significant, improves asarone sodium chloride injection product quality, improves asarone sodium chloride injection the rate of qualifiid of the lamp inspection and yield rate.
Description
Technical field
The present invention relates to a kind of improved method of asarone sodium chloride injection production technology more particularly to a kind of asarones
Sodium chloride injection deoxygenation nitrogen charging and preparation, filling process.
Background technique
Asarone sodium chloride injection specification is 100ml:16mg asarone and 0.9g sodium chloride, and prescription is asarone
0.16g/1000ml, sodium chloride 9g/1000ml, polyoxyethylene sorbitan monoleate 1.6g/1000ml.Wherein effective ingredient is asarone, is changed
Scientific name is 2,4,5- elemicins, and insoluble in water, stability is poor, light-exposed easy decomposition；The poly- mountain of pharmaceutic adjuvant
Pear ester 80 is solubilizer, and usage amount is larger, is also easy to produce foam.
The equipment registration technique is that water for injection is put into dense preparing tank, puts into chlorination sodium raw materials, and active carbon is added and (prepares
The 0.1% of volume), agitation cycle filtering decarbonization is pumped into dilute preparing tank to after clarifying；Asarone is dissolved in polyoxyethylene sorbitan monoleate,
Enter in above-mentioned same dilute preparing tank, stirs, finally add water for injection and be settled to full dose.Nitrogen charging, being stirred passes through it uniformly
Filter filtration cycle send medical fluid to filling after detection to medical fluid qualification.Lamp inspection is packed after being rolled lid, sterilizing again.Production process
In be protected from light operation as far as possible.
Asarone has preferable pharmacological activity, to bronchial asthma, chronic bronchitis, small pneumonia, the acute hair of COPD
Make and respiratory failure etc. be significant in efficacy, for total effective rate up to 85% or more, adverse reaction rate is low, while to Diplococcus pneumopniae,
The growth of staphylococcus aureus and Escherichia coli has different degrees of inhibiting effect, and safety tolerance is good, furthermore asarone
It may also suppress the release of endogenous morbid substance, and play the role of improving circulation.From this, asarone sodium chloride injection has
Wide market application prospect.
In acquirement asarone sodium chloride injection certification in 2006, the current country had the manufacturer of certification to only have for my company
Two, and only my company starts production, therefore my company's asarone sodium chloride injection has stronger competitiveness.But
The finished product rate is lower, and the rate of qualifiid of the lamp inspection is not also high, therefore need to refinement preparation, filling work on registration approval Process ba- sis
Skill improves preparation, filling process deoxygenation nitrogen filling method, and takes measures to reduce and prepare and foam volume in pouring process.
Product the rate of qualifiid of the lamp inspection and finished product rate are improved, and then reaches raising product quality, forms the mesh of stable mass production
's.
Summary of the invention
A kind of method of the present invention by improving asarone sodium chloride injection production technology, especially asarone sodium chloride
Injection deoxygenation nitrogen charging and preparation, filling process.To improve product the rate of qualifiid of the lamp inspection and finished product rate, reaches and mention
High yield quality forms stable mass production.
Technical solution of the present invention the following steps are included:
First is that improving deoxygenation nitrogen charging mode.We strengthen the deoxygenation nitrogen charging of links preparing with pouring process, match
System is filled with nitrogen protection using better way, filling using nitrogen filled protection medical fluid three times, so that asarone stable content.
Foam volume is reduced second is that taking appropriate measures, not only stable asarone content, but also reduces visible foreign matters and generate, and improve
Yield rate.
Production asarone sodium chloride injection concrete technology corrective measure has:
1, the interior water for injection of dense preparing tank (the 2# dense preparing tank in process), which cools down while using, is sufficiently filled with nitrogen under liquid level.
(water for injection not nitrogen charging in dense preparing tank when common product produces.)
2, dilute with nitrogen is filled within 5 minutes in advance in slack tank, after medical fluid is pumped into dilute preparing tank, using inflated with nitrogen on liquid level.Liquid level
Upper nitrogen charging schematic diagram sees below the preparation part in schematic diagram.(using being filled with nitrogen under liquid level when common product produces.)
3, reflux medical fluid installs stainless steel tube additional and extend under liquid level, to reduce foam volume.(phegma when common product produces
Nothing protrudes into subsurface stainless steel tube.)
4, nitrogen charging device is added to protect medical fluid again in bottle placer head tank；Medical fluid pours into after bottle and fills nitrogen twice, adjusts simultaneously
Whole nitrogen pressure >=0.2Mpa.Filling post makes every bottle liquid medicine remaining oxygen control in 3.0-4.5% range using nitrogen charging three times
It is interior.(without head tank nitrogen charging when common product produces.)
It is specific as follows:
A kind of production method of asarone sodium chloride injection, includes the following steps:
(1) chlorination sodium raw materials are squeezed into 1# dense preparing tank, the inflated with nitrogen on liquid level guarantees nitrogen pressure >=0.2MPa, nitrogen charging
Time 15-35 minute；
(2) water is squeezed into 2# dense preparing tank, the inflated with nitrogen under liquid level guarantees nitrogen pressure >=0.2MPa, nitrogen charging time 15-35
Minute；(3) 1# dense preparing tank and 2# dense preparing tank squeeze into dilute preparing tank after filtering, asarone Tween-80 solution are added to dilute
In distribution tank, the inflated with nitrogen on liquid level guarantees nitrogen pressure >=0.2MPa, continues nitrogen charging 5-10 hours；
(4) mixed solution squeezes into filling head tank after filtering in dilute preparing tank, carries out inflated with nitrogen on filling head tank liquid level,
Guarantee nitrogen pressure >=0.2MPa, continues 5-10 hours nitrogen charging time；
(5) filling head tank is further filled to each bottle, to inflated with nitrogen on each bottle of progress liquid level, guarantees nitrogen pressure
>=0.2MPa, into bottle, the inflated with nitrogen time is 8-15 seconds；
(6) to inflated with nitrogen on each bottle again nearly liquid level, guarantee nitrogen pressure >=0.2MPa, the inflated with nitrogen time into bottle
It is 2-6 seconds.In chlorination sodium raw materials, sodium chloride-containing 0.9g in every 100mL.
In asarone Tween-80 solution, 0.016g containing asarone, 0.16g containing Tween-80 in every 100mL.
1# dense preparing tank is the vertical 316L stainless cylinder of steel of 3T, 2# dense preparing tank is the vertical 316L stainless cylinder of steel of 3T, dilute preparing tank 9T
Vertical 316L stainless cylinder of steel, filling head tank are the vertical 316L stainless steel sink of 60,000 ml, bottled specification is 100ml.
On the basis of above-mentioned, further preferably following steps:
(1) chlorination sodium raw materials are squeezed into 1# dense preparing tank, the inflated with nitrogen on liquid level guarantees nitrogen pressure >=0.2MPa, nitrogen charging
Time 20 minutes, nitrogen charging tolerance was 10L；
(2) water is squeezed into 2# dense preparing tank, the inflated with nitrogen under liquid level guarantees nitrogen pressure >=0.2MPa, and the nitrogen charging time 20 divides
Clock, nitrogen charging tolerance are 10L；
(3) 1# dense preparing tank and 2# dense preparing tank squeeze into dilute preparing tank after filtering, and asarone Tween-80 solution is added to
In dilute preparing tank, the inflated with nitrogen on liquid level guarantees nitrogen pressure >=0.2MPa, continues nitrogen charging 7 hours, and nitrogen charging tolerance is 200L；
(4) mixed solution squeezes into filling head tank after filtering in dilute preparing tank, carries out inflated with nitrogen on filling head tank liquid level,
Guarantee nitrogen pressure >=0.2MPa, continue 6 hours nitrogen charging time, nitrogen charging tolerance is 180L；
(5) filling head tank is further filled to each bottle, to inflated with nitrogen on each bottle of progress liquid level, guarantees nitrogen pressure
>=0.2MPa, into bottle, the inflated with nitrogen time is 12 seconds, and nitrogen charging tolerance is 60mL；
(6) to inflated with nitrogen on each bottle again nearly liquid level, guarantee nitrogen pressure >=0.2MPa, the inflated with nitrogen time into bottle
It is 4 seconds, nitrogen charging tolerance is 20mL.
1, economic benefit
In August, 2015 in August, 2016 produces 268500 bottles of asarone sodium chloride injection altogether, and yield rate was in 2014
88% on the basis of be increased to 96.9%, accrued revenue are as follows: (every bottle by 55 yuan calculating)
268500 bottles × yuan/bottle=131.43 ten thousand yuan (96.9%-88%) × 55.
2, other comprehensive benefits
After the project implementation, plays the role of biggish to asarone sodium chloride injection product quality is improved, ensure that
The stability and consistency of product quality.It is laid the foundation simultaneously for stable prod market.
Detailed description of the invention
Fig. 1 is that asarone sodium chloride injection prepares filling process.
Fig. 2 be it is dilute match, filling post adds nitrogen structure drawing of device.
Wherein, 1-1. nitrogen supplements tank one, and 1-2 nitrogen supplements tank two, 2. injection water pots, 3. dilute preparing tanks, 4. filling height
Position slot, 5. bottle placers, 6. corking machines, 7. surge tanks.
Specific embodiment
Embodiment 1
When preparing 4,600,000 ml (4.6 ten thousand bottles), the dosage of each raw material are as follows:
Inflated with nitrogen need to guarantee nitrogen pressure 0.3MPa in sodium chloride solution in dense preparing tank, the nitrogen charging time 20 minutes, inflated with nitrogen
Amount is 10L；
Inflated with nitrogen need to guarantee nitrogen pressure 0.5MPa in water in dense preparing tank, and the nitrogen charging time 20 minutes, nitrogen charging tolerance was 10L；
Asarone tween solution inflated with nitrogen need to guarantee nitrogen pressure 0.5MPa in dilute preparing tank, continue 7 hours nitrogen charging time, fill
Nitrogen amount is 200L；
Filling first time inflated with nitrogen (head tank inflated with nitrogen) need to guarantee nitrogen pressure 0.3MPa, continue 6 hours nitrogen charging time,
Nitrogen charging tolerance is 180L；
Second of filling post inflated with nitrogen need to guarantee nitrogen pressure 0.5MPa, inflated with nitrogen time 12 seconds, inflated with nitrogen into bottle
Amount is 60ml；
Filling post third time inflated with nitrogen need to guarantee nitrogen pressure 0.3MPa, inflated with nitrogen time 4 seconds into bottle, nitrogen charging tolerance
For 20ml.
The asarone sodium chloride injection final product quality situation produced with, 2016 times in 2015 compares within 2014:
It can be seen that from upper table, 2015, asarone changes of contents is small compared with 2014 before and after sterilizing in 2016.Exist simultaneously
When production in 2014, it is filling start, midway, after our intermediate asarone content differences for monitoring away from larger, Wo Menfa
When existing foam is more, asarone content is higher, 2016 it is filling start, midway, at the end of the asarone content base taken a sample to check
This stabilization, these illustrate that the method control foam volume that we take is helpful to the content uniformity of asarone.
Claims (3)
1. a kind of production method of asarone sodium chloride injection, which comprises the steps of:
(1) chlorination sodium raw materials are squeezed into 1# dense preparing tank, the inflated with nitrogen on liquid level guarantees nitrogen pressure >=0.2MPa, nitrogen charging time
15-35 minutes, in chlorination sodium raw materials, sodium chloride-containing 0.9g in every 100mL；
(2) water is squeezed into 2# dense preparing tank, the inflated with nitrogen under liquid level guarantees that nitrogen pressure >=0.2MPa, nitrogen charging time 15-35 divide
Clock；
(3) 1# dense preparing tank and 2# dense preparing tank squeeze into dilute preparing tank after filtering, and asarone Tween-80 solution is added to dilute match
In tank, the inflated with nitrogen on liquid level guarantees nitrogen pressure >=0.2MPa, continues nitrogen charging 5-10 hours, asarone Tween-80 is molten
In liquid, 0.016g containing asarone, 0.16g containing Tween-80 in every 100mL；
(4) mixed solution squeezes into filling head tank after filtering in dilute preparing tank, carries out inflated with nitrogen on filling head tank liquid level, guarantees
Nitrogen pressure >=0.2MPa continues 5-10 hours nitrogen charging time；
(5) filling head tank is further filled to each bottle, to inflated with nitrogen on each bottle of progress liquid level, guarantee nitrogen pressure >=
0.2MPa, into bottle, the inflated with nitrogen time is 8-15 seconds；
(6) to inflated with nitrogen on each bottle again nearly liquid level, guarantee nitrogen pressure >=0.2MPa, into bottle the inflated with nitrogen time be
2-6 seconds；
Under when flowing back medical fluid, installation stainless steel tube extend into liquid level.
2. the production method of asarone sodium chloride injection described in claim 1, which is characterized in that 1# dense preparing tank is 3T
Vertical 316L stainless cylinder of steel, 2# dense preparing tank are the vertical 316L stainless cylinder of steel of 3T, dilute preparing tank be the vertical 316L stainless cylinder of steel of 9T,
Filling head tank is the vertical 316L stainless steel sink of 60,000 ml, bottled specification is 100mL.
3. the production method of asarone sodium chloride injection described in claim 2, which is characterized in that including walking as follows
It is rapid:
(1) chlorination sodium raw materials are squeezed into 1# dense preparing tank, the inflated with nitrogen on liquid level guarantees nitrogen pressure >=0.2MPa, nitrogen charging time
20 minutes, nitrogen charging tolerance was 10L；
(2) water is squeezed into 2# dense preparing tank, the inflated with nitrogen under liquid level guarantees nitrogen pressure >=0.2MPa, the nitrogen charging time 20 minutes, fills
Nitrogen amount is 10L；
(3) 1# dense preparing tank and 2# dense preparing tank squeeze into dilute preparing tank after filtering, asarone Tween-80 solution are added to dilute
In distribution tank, the inflated with nitrogen on liquid level guarantees nitrogen pressure >=0.2MPa, continues nitrogen charging 7 hours, and nitrogen charging tolerance is 200L；
(4) mixed solution squeezes into filling head tank after filtering in dilute preparing tank, carries out inflated with nitrogen on filling head tank liquid level, guarantees
Nitrogen pressure >=0.2MPa continues 6 hours nitrogen charging time, and nitrogen charging tolerance is 180L；
(5) filling head tank is further filled to each bottle, to inflated with nitrogen on each bottle of progress liquid level, guarantee nitrogen pressure >=
0.2MPa, into bottle, the inflated with nitrogen time is 12 seconds, and nitrogen charging tolerance is 60mL；
(6) to inflated with nitrogen on each bottle again nearly liquid level, guarantee nitrogen pressure >=0.2MPa, the inflated with nitrogen time is 4 into bottle
Second, nitrogen charging tolerance is 20mL；
Under when flowing back medical fluid, installation stainless steel tube extend into liquid level.
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| CN201611178976.3A CN106619498B (en) | 2016-12-19 | 2016-12-19 | A kind of production method of asarone sodium chloride injection |
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| CN201611178976.3A CN106619498B (en) | 2016-12-19 | 2016-12-19 | A kind of production method of asarone sodium chloride injection |
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Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1698590A (en) * | 2005-05-30 | 2005-11-23 | 许群 | Aarin preparation for injection and preparing process thereof |
| CN101647774A (en) * | 2009-08-31 | 2010-02-17 | 四川大学 | Asarone injection and preparation method thereof |
| CN102232931A (en) * | 2010-04-23 | 2011-11-09 | 海南中化联合制药工业股份有限公司 | Formula of asarone for injection and preparation method thereof |
| CN102973499A (en) * | 2012-12-21 | 2013-03-20 | 张蕊 | Asarone injection and preparation method thereof |
| CN105997899A (en) * | 2016-07-04 | 2016-10-12 | 海南利能康泰制药有限公司 | Asarone drug composition for injection or inhalation |
-
2016
- 2016-12-19 CN CN201611178976.3A patent/CN106619498B/en active Active
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1698590A (en) * | 2005-05-30 | 2005-11-23 | 许群 | Aarin preparation for injection and preparing process thereof |
| CN101647774A (en) * | 2009-08-31 | 2010-02-17 | 四川大学 | Asarone injection and preparation method thereof |
| CN102232931A (en) * | 2010-04-23 | 2011-11-09 | 海南中化联合制药工业股份有限公司 | Formula of asarone for injection and preparation method thereof |
| CN102973499A (en) * | 2012-12-21 | 2013-03-20 | 张蕊 | Asarone injection and preparation method thereof |
| CN105997899A (en) * | 2016-07-04 | 2016-10-12 | 海南利能康泰制药有限公司 | Asarone drug composition for injection or inhalation |
Non-Patent Citations (1)
| Title |
|---|
| 细辛脑氯化钠注射液的研究;廖娟娟;《中国优秀硕士论文全文数据库 医药卫生科技辑》;20120715;第E079-46页 |
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