CN106214627A - The preparation method of Betahistine Hydrochloride sodium chloride injection - Google Patents
The preparation method of Betahistine Hydrochloride sodium chloride injection Download PDFInfo
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- CN106214627A CN106214627A CN201610621938.4A CN201610621938A CN106214627A CN 106214627 A CN106214627 A CN 106214627A CN 201610621938 A CN201610621938 A CN 201610621938A CN 106214627 A CN106214627 A CN 106214627A
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- injection
- sodium chloride
- betahistine hydrochloride
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/08—Solutions
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- 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
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/4402—Non condensed pyridines; Hydrogenated derivatives thereof only substituted in position 2, e.g. pheniramine, bisacodyl
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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
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
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- Inorganic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention discloses the preparation method of a kind of Betahistine Hydrochloride sodium chloride injection, described injection is made up of Betahistine Hydrochloride, sodium chloride and water for injection, containing Betahistine Hydrochloride 0.05～0.08g, sodium chloride 6～10g, water for injection surplus in every 1000ml injection.The Betahistine Hydrochloride sodium chloride injection that the present invention provides can be better than improving that existing Betahistine Hydrochloride sodium chloride aqueous injection loading amount is little, use that proportioning is inconvenient, drug safety is undesirable, and liquid drugs injection needs to add preservative certain impact to human body.Not containing preservative in medicine of the present invention, stability of drug products is strong, can be used for treating auditory vertigo, also can be used for arteriosclerosis, ischemic cerebrovascular and caused by hypertension positional vertigo, tinnitus.
Description
Technical field
The invention belongs to pharmaceutical technology field, relate to the preparation method of a kind of Betahistine Hydrochloride sodium chloride injection.
Background technology
Betahistine Hydrochloride sodium chloride injection, Main Ingredients and Appearance: Betahistine Hydrochloride, adjuvant: sodium chloride, chemical name:
N-methyl-2-PEA dihydrochloride, indication: for auditory vertigo, also can be used for cerebral arteriosclerosis, ischemic brain blood
Pipe disease and caused by hypertension positional vertigo, tinnitus.The most existing Betahistine Hydrochloride aqueous injection is by hydrochloric acid
Betahistine, medicinal charcoal and water for injection composition, specification is 2ml:10mg, both can intravenous drip, it is possible to intramuscular injection, but surely
Qualitative undesirable, and liquid drugs injection needs interpolation preservative to suppress the breeding of microorganism in aqueous solution, and preservative has one to human body
Fixing sound.Also having a kind of Betahistine Hydrochloride sodium chloride injection is by Betahistine Hydrochloride, sodium chloride, medicinal charcoal and injection
Water composition, specification is 500ml: Betahistine Hydrochloride 0.02g and sodium chloride 4.5g, though stability is preferable, but loading amount is bigger
It is not easy to storage and transport and sterilising temp is low.Lyophilized injectable powder, belongs to non-final sterilising prods during production, and production is nothing
Bacterium, freezing production, use proportioning inconvenient, and tablet disintegration times is long, and dissolution and dissolution rate are low, absorption difference, biological utilisation
Spending low, supplementary product consumption ratio is big, and child, old people, bed patient and dysphagia patients take inconvenience, and compliance is poor, shadow
Ring the performance of Betahistine Hydrochloride therapeutical effect.
Summary of the invention
In order to solve the problems referred to above, the invention provides one and be applicable to intravenous Betahistine Hydrochloride sodium chloride note
Penetrate the preparation method of liquid, be used for treating auditory vertigo, also can be used for arteriosclerosis, ischemic cerebrovascular and hypertension institute
Cause positional vertigo, tinnitus.
It is an object of the invention to be achieved through the following technical solutions:
A kind of Betahistine Hydrochloride sodium chloride injection, by Betahistine Hydrochloride, sodium chloride, activated carbon (pin is used) and water for injection
Composition, containing Betahistine Hydrochloride 0.05～0.08g, sodium chloride 6～10g, activated carbon (pin is used) 0.1 in every 1000ml injection
～1g, water for injection surplus.
The preparation method of a kind of above-mentioned Betahistine Hydrochloride sodium chloride injection, comprises the steps:
One, pretreatment of raw material: accurately weigh the Betahistine Hydrochloride of amount of preparation in beaker, adds a small amount of water for injection and dissolves, join
Become 40～60wt% concentrated solutions, pour in 250ml infusion bottle, lid plug, roll lid, 121 DEG C of sterilizings 9 minutes, take out standby.
Two, dense join: in dense preparing tank, add preparation cumulative volume 4～the water for injection of 6%, be cooled to 45 ± 5 DEG C, by sterilizing
After Betahistine Hydrochloride concentrated solution be dissolved in wherein, with 75～85r/min rotating speeds stir 5～15 minutes, through 0.45 m titanium rod mistake
Filter is filtered to distribution tank；In another dense preparing tank, add appropriate water for injection, be heated to 90 ± 5 DEG C, add sodium chloride and be made into 20
～30wt% concentrated solution, add activated carbon (pin is used), stir 5～15 minutes with 75～85r/min rotating speeds, boil 5～15 minutes,
It is cooled to 45 ± 5 DEG C, in 0.45 m titanium rod filter filter to dilute preparing tank.
Three, dilute join: mend and inject water to prepare cumulative volume, stir 20～40 minutes with 80～85r/min rotating speeds, simultaneously
It is cooled to 35 ± 5 DEG C, adjusts pH value 4.5～5.0, survey content, pH value to meet intermediate products quality standard with 5moI/L sodium hydroxide,
Filter through 0.45 m titanium rod, 0.22 m cylindrical filter cartridge filter filters.
Four, check the qualified rear fill of visible foreign matters, tamponade, roll lid, 121 DEG C of sterilizings 9 minutes, packaging after lamp inspection is qualified.
Activated carbon (pin with) takes 180 DEG C, the activation method of 4 hours dry heat sterilizations before use, produces and carries out the previous day
Activation processing, activating amount is the usage amount of a day, and the longest resting period of the activated carbon (pin is used) after activation is little less than 36
Time, activation should be re-started as exceeded.
Present invention have the advantage that
1, Betahistine Hydrochloride raw material of the present invention is before formal production process, needs to carry out raw material and anticipates, through pretreatment
After crude drug clarity limpider, it is possible to reduce the microorganism of crude drug is polluted, during to ensure to produce normal and increase lamp
Inspection qualification rate, the benefit improving production and the safety of medicine.
2, the Betahistine Hydrochloride sodium chloride injection that the present invention provides can be effectively improved existing Betahistine Hydrochloride chlorine
Change sodium aqueous injection loading amount is little, use proportioning inconvenience, stability of drug products undesirable, and liquid drugs injection needs to add preservative to be had human body
Certain impact.
3, not containing preservative in medicine of the present invention, stability of drug products is strong.
4, the invention belongs to the medicine of sterile production, production environment and operator are required strictly, it is necessary to entered specialty
Training just can on duty operate, and through 121 DEG C of high temperature sterilizes 9 minutes, with further up to the effect eliminating germ contamination, it is ensured that
The safety of medicine and stability.
Detailed description of the invention
Below in conjunction with embodiment, technical scheme is further described, but is not limited thereto, every right
Technical solution of the present invention is modified or equivalent, without deviating from the spirit and scope of technical solution of the present invention, all should contain
Cover in protection scope of the present invention.
Embodiment 1:
A kind of Betahistine Hydrochloride sodium chloride injection, by Betahistine Hydrochloride, sodium chloride, activated carbon (pin is used) and water for injection
Composition, containing Betahistine Hydrochloride 0.08g, sodium chloride 9g, activated carbon (pin is used) 0.6g, water for injection in every 1000ml injection
Surplus.
The preparation method of above-mentioned Betahistine Hydrochloride sodium chloride injection, comprises the steps:
One, pretreatment of raw material: accurately weigh the Betahistine Hydrochloride of amount of preparation in beaker, adds a small amount of water for injection and dissolves, join
Become 50wt% concentrated solution, pour in 250ml infusion bottle, lid plug, roll lid, 121 DEG C of sterilizings 9 minutes, standby；Pretreated salt
Acid betahistine concentrated solution uses after sterilization for 7 days.
Two, dense join: in dense preparing tank, add the water for injection of preparation cumulative volume 5%, be cooled to 45 ± 5 DEG C, after sterilizing
Betahistine Hydrochloride concentrated solution is dissolved in wherein, stirs 10 minutes with 81r/min rotating speed, filters to distribution tank through 0.45 m titanium rod filter
In；Adding appropriate water for injection in another dense preparing tank, be heated to 90 ± 5 DEG C, it is dense molten that addition sodium chloride is made into 20～30wt%
Liquid, adds activated carbon (pin is used), stirs 10 minutes with 81r/min rotating speed, boil 10 minutes, be cooled to 45 ± 5 DEG C, through 0.45 m
Titanium rod filter is filtered to distribution tank.
Three, dilute join: mend and inject water to prepare cumulative volume, stir 30 minutes with 83r/min rotating speed, be cooled to 35 simultaneously
± 5 DEG C, pH value 4.5～5.0, survey content, pH value is adjusted to meet intermediate products quality standard with 5moI/L sodium hydroxide.
Four, check the qualified rear fill of visible foreign matters, tamponade, roll lid, 121 DEG C of sterilizings 9 minutes, packaging after lamp inspection is qualified.
Clinical data
Physical data: male 16 examples, female 18 example, age 40～72 years old, all there is unexpected dizziness, regarding thing rotation, nausea and vomiting, tinnitus,
Companion pale complexion, perspiration, nystagmus symptom.Disease time 30min～24h.34 example cases are randomly divided into two groups, treatment group 20 example,
Matched group 14 example.
Therapeutic Method: the Betahistine Hydrochloride sodium chloride injection 250ml of quiet the present embodiment for the treatment of group, matched group gives 5%
Glucose injection 250ml, adds mountain Liang alkali 10mg, vitamin C 1.0g vitamin B6100mg, coenzyme A 100u, every day 1 time, see
Examine 2 days.
Outcome measure: recovery from illness: dizziness and simultaneous phenomenon all disappear；Effective: dizziness and simultaneous phenomenon reduce more than 2；
Progressive: dizziness and simultaneous phenomenon improve 1；Invalid: dizziness and simultaneous phenomenon are without improving.
Result: two groups of observation of curative effect, treatment group fully recovers 12 examples (60%), effective 7 examples (35%), and further 1 example (5%) is invalid
0 example；Matched group is fully recovered 3 examples (21.5%), effective 7 examples (35.7%), progressive 3 examples (21.5%), invalid 1 example (7%).Improve after transfusion
Time, treatment group 1～6h, average 3.5h；Matched group 3 ~ 12h, average 8h.
Untoward reaction: two groups of untoward reaction are compared, treatment group 2 example accounts for 10%, and symptom is relatively light, holds time short, infusion-completed
Average 35min disappears；Matched group untoward reaction 13 example, accounts for 92.8%, and symptom is relatively light, holds time longer, and average extinction time is
4.5h is finished in transfusion.
Discuss: betahistine is H1Receptor stimulating agent, particularly has brighter to Arterial system at the bottom of vertebra to cerebrovascular, cardiovascular
Aobvious dilating effect.Dramatically increase heart and brain and surrounding loop blood flow, improve microcirculation, increase cochlea and submarine blood flow, fall
Low venae auditivae internae pressure and promotion Lymphatic, thus eliminate auditory vertigo, tinnitus and deafness sense.Increase blood capillary to lead to simultaneously
Property thoroughly, promotes the absorption of extracellular fluid, eliminates edema in lymph, increases the stability of blood capillary, and untoward reaction is few, uses
Safer.
Embodiment 2:
The present embodiment is as different from Example 1: in every 1000ml injection containing Betahistine Hydrochloride 0.05g, sodium chloride 7g,
Activated carbon (pin is used) 0.5g, water for injection surplus.
Embodiment 3:
The present embodiment is as different from Example 1: in every 1000ml injection containing Betahistine Hydrochloride 0.08g, sodium chloride 8g,
Activated carbon (pin is used) 0.8g, water for injection surplus.
Claims (10)
1. a Betahistine Hydrochloride sodium chloride injection, it is characterised in that described injection by Betahistine Hydrochloride, sodium chloride,
Needle-use activated carbon and water for injection composition, containing Betahistine Hydrochloride 0.05～0.08g, sodium chloride 6 in every 1000ml injection
～10g, needle-use activated carbon 0.1 ~ 1g, water for injection surplus.
Betahistine Hydrochloride sodium chloride injection the most according to claim 1, it is characterised in that in every 1000ml injection
Containing Betahistine Hydrochloride 0.08g, sodium chloride 9g, needle-use activated carbon 0.6g, water for injection surplus.
Betahistine Hydrochloride sodium chloride injection the most according to claim 1, it is characterised in that in every 1000ml injection
Containing Betahistine Hydrochloride 0.05g, sodium chloride 7g, needle-use activated carbon 0.5g, water for injection surplus.
Betahistine Hydrochloride sodium chloride injection the most according to claim 1, it is characterised in that in every 1000ml injection
Containing Betahistine Hydrochloride 0.08g, sodium chloride 8g, needle-use activated carbon 0.8g, water for injection surplus.
5. a preparation method for Betahistine Hydrochloride sodium chloride injection described in claim 1-4 any claim, it is special
Levy and be that described preparation method step is as follows:
One, pretreatment of raw material: accurately weigh the Betahistine Hydrochloride of amount of preparation in beaker, be dissolved in water for injection, be made into 40
～60wt% concentrated solution, pour in 250ml infusion bottle, lid plug, roll lid, sterilizing, take out standby；
Two, dense join: in dense preparing tank, add preparation cumulative volume 4～the water for injection of 6%, be cooled to 45 ± 5 DEG C, after sterilizing
Betahistine Hydrochloride concentrated solution is dissolved in wherein, stirs 5～15 minutes with 75～85r/min rotating speeds, filters to joining through titanium rod filter
In tank；In another dense preparing tank, add water for injection, be heated to 90 ± 5 DEG C, add sodium chloride and be made into 20～30wt% concentrated solutions,
Add needle-use activated carbon, stir 5～15 minutes with 75～85r/min rotating speeds, boil 5～15 minutes, be cooled to 45 ± 5 DEG C, warp
Titanium rod filter is filtered to distribution tank；
Three, dilute join: mend and inject water to prepare cumulative volume, stir 20～40 minutes with 80～85r/min rotating speeds, cool down simultaneously
To 35 ± 5 DEG C, pH value 4.5～5.0, survey content, pH value is adjusted to meet intermediate products quality standard, through titanium rod mistake with sodium hydroxide
Filter, cylindrical filter cartridge filter filter；
Four, check the qualified rear fill of visible foreign matters, tamponade, roll lid, sterilizing, packaging after lamp inspection is qualified.
The preparation method of Betahistine Hydrochloride sodium chloride injection the most according to claim 5, it is characterised in that described in go out
Betahistine Hydrochloride concentrated solution after bacterium uses for 7 days.
The preparation method of Betahistine Hydrochloride sodium chloride injection the most according to claim 5, it is characterised in that described titanium
The aperture of rod filter is 0.45 m.
The preparation method of Betahistine Hydrochloride sodium chloride injection the most according to claim 5, it is characterised in that described cylinder
The aperture of formula candle filter is 0.22 m.
The preparation method of Betahistine Hydrochloride sodium chloride injection the most according to claim 5, it is characterised in that described pin
180 DEG C, 4 hours dry heat sterilizations is taked before use with activated carbon.
The preparation method of Betahistine Hydrochloride sodium chloride injection the most according to claim 5, it is characterised in that described in go out
Bacterium temperature 121 DEG C, 9 minutes time.
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610621938.4A CN106214627A (en) | 2016-08-02 | 2016-08-02 | The preparation method of Betahistine Hydrochloride sodium chloride injection |
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| CN201610621938.4A CN106214627A (en) | 2016-08-02 | 2016-08-02 | The preparation method of Betahistine Hydrochloride sodium chloride injection |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN117476120A (en) * | 2023-10-23 | 2024-01-30 | 黑龙江中桂制药有限公司 | Synthesis method of betahistine hydrochloride, normalization evaluation method and device of synthesis parameters |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1732934A (en) * | 2005-08-10 | 2006-02-15 | 陈学峰 | Freeze dry betahistine hydrochloride injection and method for preparing the same |
| CN102366400A (en) * | 2011-09-28 | 2012-03-07 | 河南辅仁怀庆堂制药有限公司 | Betahistine hydrochloride injection and its production technology |
-
2016
- 2016-08-02 CN CN201610621938.4A patent/CN106214627A/en active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1732934A (en) * | 2005-08-10 | 2006-02-15 | 陈学峰 | Freeze dry betahistine hydrochloride injection and method for preparing the same |
| CN102366400A (en) * | 2011-09-28 | 2012-03-07 | 河南辅仁怀庆堂制药有限公司 | Betahistine hydrochloride injection and its production technology |
Non-Patent Citations (1)
| Title |
|---|
| 陈卫卫等: "《药剂学》", 31 January 2014, 西安交通大学出版社 * |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN117476120A (en) * | 2023-10-23 | 2024-01-30 | 黑龙江中桂制药有限公司 | Synthesis method of betahistine hydrochloride, normalization evaluation method and device of synthesis parameters |
| CN117476120B (en) * | 2023-10-23 | 2024-05-03 | 黑龙江中桂制药有限公司 | Synthesis method of betahistine hydrochloride, normalization evaluation method and device of synthesis parameters |
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Application publication date: 20161214 |