CN106389347A - Applications of glacial acetic acid in freeze drying process of dianhydrodulcitol or composition thereof - Google Patents
Applications of glacial acetic acid in freeze drying process of dianhydrodulcitol or composition thereof Download PDFInfo
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- CN106389347A CN106389347A CN201510452601.0A CN201510452601A CN106389347A CN 106389347 A CN106389347 A CN 106389347A CN 201510452601 A CN201510452601 A CN 201510452601A CN 106389347 A CN106389347 A CN 106389347A
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Abstract
The present invention relates to applications of glacial acetic acid in a loose dry product preparation process using freeze drying of dianhydrodulcitol or a composition thereof. According to the present invention, by using the dissolving medium and the preparation method thereof, drying is performed according to the predetermined freeze-drying process to obtain the freeze drying product of the dianhydrodulcitol or the composition thereof, the freeze drying product is the loose amorphous body, the melting point is not changed after the freeze drying product is stored for 200 days at a room temperature in a sealed manner, and the quality stability of the freeze drying product of the present invention is significantly superior to the quality stability of the dianhydrodulcitol or composition freeze drying powder prepared in the prior art.
Description
Technical field
The present invention relates to chemical medicine field is and in particular to glacial acetic acid adopts freeze-drying in dianhydrogalactitol or combinations thereof
Make the application during loose drying thing.
Background technology
(1,2-5,6-Dianhydrog alactito.DAD is hexitol kind anti-cancer drugs to 1,2-5,6 two dehydration dulcitols, also known as going
Water dulcitol (C6H10O4), NSC-132313, dianhydrogalactitol, DAG.【Outer literary fame】Dianhydrogalactitol.
It is anticarcinogen 1, the converted product of 6- mitolactol, there is preferable short term effect to chronic granulocytes leukemia, remission rate is 86%.
Also there is certain curative effect to lung cancer, Huppert's disease, nasopharyngeal carcinoma etc., efficient to various lung cancer, it is only below mustargen, silk
Rimocidin C and methopterin, but toxicity is then lighter.
Dianhydrogalactitol has broad-spectrum anti-tumor activity to the transplanted tumor of animal.Clinical research proves to chronic granulocyte white blood
Sick (slow grain) has preferable short term effect, and remission rate is 86.0%, and markedly fast, beautiful with the busulfan of document report and indigo
Red comparison, remission rate and busulfan are close and be higher than indigo red, but complete remission rate is less than busulfan.DAD effective compared with other
Two medicines are fast, and side effect is lighter than busulfan, with busulfan no crossing drug resistant, can promote the use of as inducer remission medicine.
In addition dianhydrogalactitol compares with to the medicine of lung cancer and other pernicious breast tumor, is only second to mustargen to the curative effect of gland cancer,
Mitomycin C and methotrexate (MTX) and marrow, more above-mentioned two medicines of the toxicity such as alimentary canal and liver kidney are light.To Huppert's disease
Efficient 55.6%, remaining clinical symptoms is improved, and ostalgia substantially mitigates, and also has certain curative effect to thick liquid cell Huppert's disease,
Thus have the value researching and developing further.
Due to the restriction of existing lyophilized technique, the fusing point between dianhydrogalactitol dried frozen aquatic products every batch, water-soluble and fat-soluble presence
Huge difference, for the problems referred to above, by improving lyophilized technique, improves the stability of product it is proposed that the present invention.
Content of the invention
It is an object of the invention to provide glacial acetic acid made using non-aqueous freeze-drying in dianhydrogalactitol or combinations thereof loose
Application during dried object.
Preferably, glacial acetic acid water content of the present invention is not higher than 5%.
Preferably, in dianhydrogalactitol of the present invention or combinations thereof, 1,2-5,6 NSC-132313 contents are 5%～
100%.
It is a further object of the present invention to provide glacial acetic acid is made using non-aqueous freeze-drying in dianhydrogalactitol or combinations thereof
Non-aqueous freeze-drying step during loose drying thing.
Non-aqueous freeze-drying of the present invention includes non-aqueous preparation and two steps of freeze-drying.
Non-aqueous preparation of the present invention comprises the following steps：Dianhydrogalactitol or combinations thereof ice acetic acid liquid is taken to make dissolving,
Make the solution being 0.5%～20% containing dianhydrogalactitol.
Preferably, during non-aqueous preparation of the present invention, solution temperature is 20 DEG C～50 DEG C.
Freeze-drying of the present invention comprises the steps：
1) pre-freeze：Dianhydrogalactitol or combinations thereof ice acetic acid are made dissolving, filtration, filtrate dispenses to open containers,
Be placed in lyophilized cabinet, in 0.25h～5h continued down to 10 DEG C～-5 DEG C, and this temperature maintain 0.25h～5h；
2) freeze and system balancing：After pre-freeze is terminated, continued down within the time of 0.25h～5h, by lyophilized cabinet interior temperature
Degree be down to -3 DEG C～-80 DEG C, and at -3 DEG C～-80 DEG C maintain 0.25h～5h, then maintain temperature-resistant by lyophilized cabinet
Pressure is adjusted to 2Pa～10Pa, maintains 0.5～5h；
3) distil：It is passed through sterile steam or gas makes vacuum be promoted to 20Pa～150Pa, keep 0.25h～10h；
Continue to be passed through sterile steam or gas makes vacuum in 30Pa～150Pa, by flaggy temperature in lyophilized cabinet by basal temperature -3
DEG C～-80 DEG C be promoted to 10 DEG C～-2 DEG C in 0.5～5h, and be maintained at this temperature 0.5～5h；
4) parse：After distillation terminates, change and be passed through aseptic gas and make vacuum in 30Pa～150Pa, flaggy in the lyophilized cabinet of adjustment
Temperature is 20 DEG C～40 DEG C, and maintains 0.5h～10h with this understanding；
5) it is lyophilized and terminate：After lyophilized in-cabinet temperature reaches 20 DEG C and at least two product temperatures are popped one's head in more than 20 DEG C, adjustment
Vacuum in lyophilized cabinet to 0.1Pa～5Pa and keeps 1～10h, terminates lyophilized operation, opens cabinet door, discharging.
The present invention provide non-aqueous freeze-drying prepare dianhydrogalactitol loose drying thing or combinations thereof, this application have with
Lower advantage：
1st, the dianhydrogalactitol loose drying body that the present invention makes, fusing point is 101.5 ± 2 DEG C；After putting 40 DEG C of placement 7d, fusing point
No reduce, add water or be settled solution during anhydrous alcohol solution, no precipitation generates, steady quality.
Document report, the fusing point of dianhydrogalactitol crystallization is 95.5～102.5 DEG C, but for dianhydrogalactitol freeze-dried powder, then not
See the requirement having fusing point test.When preparing dianhydrogalactitol loose drying body, such as in preparation process, choosing uses water as dissolving medium,
The fusing point of products obtained therefrom generally drops to 76～95 DEG C；Put 40 DEG C place 7d after, add water or be respectively formed breast during anhydrous alcohol solution
Shape turbid solution, precipitation does not dissolve in acetone.
Products obtained therefrom of the present invention remains the product appearance good moldability with water for solvent gained, that is, have spongy bulk knot
Structure, no duricrust, atrophy, subside, ash dissipate etc. phenomenon advantage.
2nd, " the freeze-drying research of organic solvent " (food industry is scientific and technological, Vol.27, No.05,2006), discloses the tert-butyl alcohol
Because having high-melting-point, high-vapor-pressure, therefore can be used as preferable freezing solvent.In addition, a small amount of tert-butyl alcohol is added to water
The crystal habit of water in solution, can be changed when freezing, form acicular crystal, be more beneficial for the volatilization of water, therefore current
Study hotspot is tertiary butanol and water cosolvent.The technical problem that the open source literature tert-butyl alcohol solves in lyophilized is：(a) biological system
Product are insoluble in water or its aqueous solution is unstable；B () improves rate of drying.
Present subject matter is to advocate non-aqueous freeze-drying, replaces water with glacial acetic acid more than 95% for the purity content, keeps away as far as possible
Exempt from water and participate in whole freeze-drying process, thus avoiding product that water degradation reaction occurs.
3rd, have no the open source literature that glacial acetic acid uses in freeze-drying process at present.The present invention is in freeze-drying process using glacial acetic acid
Purpose is dissolving dianhydrogalactitol, and avoids dianhydrogalactitol to generate in freezing dry process enlivening crystal formation, thus solving
Stablize poor problem between product storage life.
4th, the present invention, according to itself inherent feature of dianhydrogalactitol, works out the cold of suitable dianhydrogalactitol and combinations thereof
Freeze drying parameter, prepare products obtained therefrom with the freeze-drying method that the present invention limits, remove water with existing freeze-drying method gained
Dulcitol freeze-drying prods are compared, and improve the quality stability of long-time preservation.The different freeze-drying method products obtained therefrom of contrast
Fusing point can learn：The fusing point of products obtained therefrom of the present invention is 101 DEG C about, through the accelerated stability test of 3 months,
Sample fusing point is unchanged.The fusing point of comparative example products obtained therefrom is 94～96 DEG C, through the accelerated stability test of 3 months, sample
Product fusing point is all decreased significantly to 83～86 DEG C.
Fusing point is an a kind of physical property of material, in organic chemistry filed, for organic compound purely, typically
There is definite melting point.In the case that pressure is fixing, its fusing point is indeclinable.But work as and contain other compositions in this material,
There is large change in the fusing point that can make this material, therefore, the present invention confirms dianhydrogalactitol by measuring the fusing point of product
Stability.From experimental result it is known that freeze-drying method gained dianhydrogalactitol steady quality of the present invention, either
Fusing point contrast after difference between every batch during preparation, or acceleration, all highly stable.Comparative example products obtained therefrom is not only just
Differ greatly between every batch when preparing, after accelerated test, by measuring fusing point it can be appreciated that its product quality is sent out
Given birth to conspicuousness change, impurity apparently higher than before accelerated test data it was demonstrated that its product extremely unstable.
5th, the method for preparing freeze-dried powder that the present invention provides, is suitable for non-water law lyophilisation product, selected glacial acetic acid
Solvent toxicity is close with ethanol, to freeze-drier in addition to attention is explosion-proof, no other particular/special requirements.By the freeze-drying work being given
Skill, the organic solvent residual total amount of products obtained therefrom is not higher than 0.001%, and products obtained therefrom condition is good, no obvious with water dried frozen aquatic products
Difference.
Specific embodiment
Further illustrate the present invention below by embodiment.It should be understood that embodiments of the invention are for this is described
Bright rather than limitation of the present invention.Broadly fall into application claims according to the simple modifications that the essence of the present invention is carried out to the present invention
The scope of protection.Unless otherwise stated, the percent concentration in the present invention is solute percentage by volume, and g/v represents solution
Solute volume ratio.
Embodiment 1：Dianhydrogalactitol freeze-dried powder
Weigh dianhydrogalactitol, operate in the steps below：
1) pre-freeze：The glacial acetic acid that dianhydrogalactitol addition water content is 5%, 0.5% solution is made in dissolving at 20 DEG C,
Filtration, filtrate dispenses to open containers, is placed in lyophilized cabinet, in 0.25h continued down to 10 DEG C, and in this temperature
Maintain 0.25h；
2) freeze and system balancing：After pre-freeze is terminated, continued down within the time of 0.25h, lyophilized in-cabinet temperature is dropped
To -3 DEG C, and maintain 0.25h at this temperature, then the lyophilized in-cabinet temperature of maintenance is constant, and adjustment vacuum is 2Pa, and protects
Hold 0.5h；
3) distil：It is passed through sterile steam or gas makes vacuum be promoted to 150Pa, keep 0.25h；
Continue to be passed through sterile steam or gas makes vacuum in 150Pa, flaggy temperature in lyophilized cabinet is existed by -3 DEG C of basal temperature
It is promoted to -2 DEG C in 0.5h, and be maintained at this temperature 0.5h；
4) parse：After distillation terminates, change and be passed through aseptic gas and make vacuum in 150Pa, in the lyophilized cabinet of adjustment, flaggy temperature is
20 DEG C, and maintain 0.5h with this understanding；
5) it is lyophilized and terminate：After lyophilized in-cabinet temperature reaches 20 DEG C and at least two product temperatures are popped one's head in more than 20 DEG C, adjustment
Vacuum in lyophilized cabinet to 0.1Pa and keeps 1h, terminates lyophilized operation, opens cabinet door, discharging.
Above operation repeats three batches.After testing, glacial acetic acid residual quantity is 0.001%, 0.001%, 0.001%, 1,2-5,6
NSC-132313 content is 100%, 99.8%, 99.7%.
Embodiment 2：Dianhydrogalactitol freeze-dried powder
1) pre-freeze：It is 3% glacial acetic acid that dianhydrogalactitol is added water content, and 10% solution is made in dissolving at 30 DEG C, filters,
Filtrate dispenses to open containers, is placed in lyophilized cabinet, in 3h continued down to 0 DEG C, and this temperature maintain 3h；
2) freeze and system balancing：After pre-freeze is terminated, continued down within the time of 3h, lyophilized in-cabinet temperature is down to
- 40 DEG C, and maintain 3h at this temperature, then the lyophilized in-cabinet temperature of maintenance is constant, and adjustment vacuum is 5Pa, and keeps 3h；
3) distil：It is passed through sterile steam or gas makes vacuum be promoted to 80Pa, keep 3h；
Continue to be passed through sterile steam or gas makes vacuum in 100Pa, flaggy temperature in lyophilized cabinet is existed by -40 DEG C of basal temperature
It is promoted to 5 DEG C in 3h, and be maintained at this temperature 3h；
4) parse：After distillation terminates, change and be passed through aseptic gas and make vacuum in 100Pa, in the lyophilized cabinet of adjustment, flaggy temperature is
30 DEG C, and maintain 5h with this understanding；
5) it is lyophilized and terminate：After lyophilized in-cabinet temperature reaches 20 DEG C and at least two product temperatures are popped one's head in more than 20 DEG C, adjustment
Vacuum in lyophilized cabinet to 3Pa and keeps 5h, terminates lyophilized operation, opens cabinet door, discharging.
Above operation repeats three batches.After testing, glacial acetic acid residual quantity is 0.00096%, 0.00089%, 0.00092%,
1,2-5,6 NSC-132313 content is 50.0%, 50.2%, 50.5%.
Embodiment 3：Dianhydrogalactitol composition freeze-dried powder
Weigh dianhydrogalactitol, operate in the steps below：
1) pre-freeze：It is in 1% glacial acetic acid that dianhydrogalactitol and PVP (PVP) are added water content, dissolves at 50 DEG C
Make the solution containing 20% dianhydrogalactitol, filtration, filtrate dispenses to open containers, is placed in lyophilized cabinet, holds in 5h
Continue and be cooled to -5 DEG C, and maintain 5h in this temperature；
2) freeze and system balancing：After pre-freeze is terminated, continued down within the time of 5h, lyophilized in-cabinet temperature is down to
- 80 DEG C, and maintain 5h at this temperature, then the lyophilized in-cabinet temperature of maintenance is constant, and adjustment vacuum is 10Pa, and keeps
5h；
3) distil：Being passed through sterile steam makes vacuum in 20Pa, keeps 10h；
Continue to be passed through sterile steam or gas make vacuum in 30Pa, by flaggy temperature in lyophilized cabinet by -80 DEG C of basal temperature
It is promoted to 10 DEG C in 5h, and be maintained at this temperature 5h；
4) parse：After distillation terminates, change and be passed through aseptic gas and make vacuum in 30Pa, in the lyophilized cabinet of adjustment, flaggy temperature is
40 DEG C, and maintain 10h with this understanding；
5) it is lyophilized and terminate：After lyophilized in-cabinet temperature reaches 20 DEG C and at least two product temperatures are popped one's head in more than 20 DEG C, adjustment
Vacuum in lyophilized cabinet to 5Pa and keeps 10h, terminates lyophilized operation, opens cabinet door, discharging.
Above operation repeats three batches.After testing, glacial acetic acid residual quantity is 0.0009%, 0.0008%, 0.0009%, 1,2-5,6
NSC-132313 content is 5.0%, 5.6%, 5.3%.
Comparative example 1：It is that dianhydrogalactitol freeze-dried powder prepared by solvent with water
Weigh dianhydrogalactitol, operate in the steps below：
1) pre-freeze：Dianhydrogalactitol is added to the water, 0.5% solution, filtration are made in dissolving at 20 DEG C, and filtrate dispenses
To open containers, be placed in lyophilized cabinet, in 0.25h continued down to 10 DEG C, and this temperature maintain 0.25h；
2) freeze and system balancing：After pre-freeze is terminated, continued down within the time of 0.25h, lyophilized in-cabinet temperature is dropped
To -3 DEG C, and maintain 0.25h at this temperature, then remain temperature-resistant and pressure in lyophilized cabinet is adjusted to 2Pa, maintain
0.5h；
3) distil：It is passed through sterile steam or gas makes vacuum be promoted to 150Pa, keep 0.25h；
Continue to be passed through sterile steam or gas makes vacuum in 150Pa, flaggy temperature in lyophilized cabinet is existed by -3 DEG C of basal temperature
It is promoted to -2 DEG C in 0.5h, and be maintained at this temperature 0.5h；
4) parse：After distillation terminates, change and be passed through aseptic gas and make vacuum in 150Pa, in the lyophilized cabinet of adjustment, flaggy temperature is
20 DEG C, and maintain 0.5h with this understanding；
5) it is lyophilized and terminate：After lyophilized in-cabinet temperature reaches 20 DEG C and at least two product temperatures are popped one's head in more than 20 DEG C, adjustment is frozen
Vacuum in dry cabinet to 0.1Pa and keeps 1h, terminates lyophilized operation, opens cabinet door, discharging.
Above operation repeats three batches.After testing, 1,2-5,6 NSC-132313 contents are 95.5%, 95.8%, 95.6%.
Comparative example 2：The different freeze-drying curve of adjustment prepares dianhydrogalactitol freeze-dried powder
Weigh dianhydrogalactitol, operate in the steps below：
1) pre-freeze：Dianhydrogalactitol ice acetic acid is made dissolving make 5% solution, filtration, filtrate dispenses to open containers
In, it is placed in lyophilized cabinet, in 1h, continued down, to 11 DEG C, and maintains this in temperature 1.5h；
2) freeze and system balancing：After pre-freeze is terminated, continued down within the time of 1.5h, lyophilized in-cabinet temperature is dropped
To -2 DEG C, and maintain 1.5h at this temperature, then remain temperature-resistant and pressure in lyophilized cabinet is adjusted to 160Pa, dimension
Hold 1h；
3) distil：Maintain vacuum in 160Pa, flaggy temperature in lyophilized cabinet is promoted to 11 DEG C for -2 DEG C by basal temperature, and
It is maintained at this temperature 6h；Then the lyophilized in-cabinet temperature of maintenance is constant, and adjustment vacuum is 160Pa, and keeps 1h；
4) parse：After distillation terminates, in the lyophilized cabinet of adjustment flaggy temperature be 50 DEG C, vacuum be 160Pa, and in this condition
Lower maintenance 6h；
5) it is lyophilized and terminate：After lyophilized in-cabinet temperature reaches 50 DEG C and at least two product temperatures are popped one's head in more than 50 DEG C, adjustment
Vacuum in lyophilized cabinet to 3Pa and keeps 3h, terminates lyophilized operation, opens cabinet door, discharging.
Above operation repeats three batches.After testing, glacial acetic acid residual quantity is 3.8%, 3.9%, 3.75%, and 1,2-5,6 two go
Water winged euonymus alcohol content is 96.4%, 96.0%, 96.8%.
The dianhydrogalactitol freeze dried powder of distinct methods preparation compares
1st, the dianhydrogalactitol freeze-drying effect and fusing point of embodiment 1-4 and comparative example 1-2 is compared, knot
Fruit is shown in Table 1.
Table 1：The drying regime of dianhydrogalactitol freeze-dried powder compares
| Sample fusing point | Solubility in water | Solubility in absolute ethyl alcohol | |
| Embodiment 1 | 101.2±0.5℃ | Dissolving, clarification | Dissolving, clarification |
| Embodiment 2 | 101.3±0.7℃ | Dissolving, clarification | Dissolving, clarification |
| Embodiment 3 | / | Dissolving, clarification | Dissolving, clarification |
| Comparative example 1 | 95.8±1.1℃ | Micro- muddy | Muddy |
| Comparative example 2 | 94.1±1.3℃ | Dissolving, clarification | Dissolving, clarification |
2nd, temperature be 40 DEG C, humidity be 75% under carry out accelerated stability test, the testing result after 3 months is shown in Table 2.
Table 2：Dianhydrogalactitol freeze-dried powder acceleration for stabilization result of the test compares
| Sample fusing point (DEG C) | Solubility in water | Solubility in absolute ethyl alcohol | |
| Embodiment 1 | 101.5±1℃ | Dissolving, clarification | Dissolving, clarification |
| Embodiment 2 | 101.4±1℃ | Dissolving, clarification | Dissolving, clarification |
| Embodiment 3 | / | Dissolving, clarification | Dissolving, clarification |
| Comparative example 1 | 85.8±1.1℃ | Muddy | Muddy |
| Comparative example 2 | 83.5±1℃ | Dissolving, clarification | Dissolving, clarification |
Conclusion：As can be seen from Table 1, the fusing point using preparation method gained sample of the present invention is higher than comparative example.Accelerate
After stability test 3 months, table 2 result shows, before and after accelerated test, the sample fusing point of the present invention has almost no change, card
Its material bright is consistent with when just preparing, steady quality；And although comparative example 1 employs identical freeze-drying curve,
But the use of water is solvent, although comparative example 2-3 is solvent all using glacial acetic acid, not using the freeze-drying curve of present invention restriction,
Solvent residual amount is far above embodiment, and after the accelerated test of sample, its fusing point all has different degrees of change it was demonstrated that preserving
During, sample there occurs the change of essence.
From above-mentioned test, dianhydrogalactitol freeze-dried powder be a kind of material of extremely unstable although unclear producing or
During depositing, what the details that dianhydrogalactitol changes and the impurity ultimately forming is, but inventor passes through control
Freeze-drying process processed, the fusing point controlling product, when 99.5-103.5 DEG C, can make product keep steady quality.
Although, above use general explanation, specific embodiment and test, the present invention is described in detail,
But on the basis of the present invention, it can be made some modifications or improvements, this will be apparent to those skilled in the art.
Therefore, these modifications or improvements without departing from theon the basis of the spirit of the present invention, belong to claimed model
Enclose.
Claims (7)
1. glacial acetic acid makes the application during loose drying thing in dianhydrogalactitol or combinations thereof using non-aqueous freeze-drying.
2. application as claimed in claim 1 is it is characterised in that glacial acetic acid water content is not higher than 5%.
3. application as claimed in claim 1 is it is characterised in that in dianhydrogalactitol or combinations thereof, 1,2-5,6 NSC-132313 contents are 5%～100%.
4. application as claimed in claim 1 is it is characterised in that non-aqueous freeze-drying includes non-aqueous preparation and two steps of freeze-drying.
5. application as claimed in claim 4 is it is characterised in that non-aqueous preparation comprises the following steps：Take dianhydrogalactitol or combinations thereof ice acetic acid liquid to make dissolving, make the solution being 0.5%～20% containing dianhydrogalactitol.
6. as claimed in claim 4 application it is characterised in that non-aqueous prepare when solution temperature be 20 DEG C～50 DEG C.
7. application as claimed in claim 4 is it is characterised in that freeze-drying comprises the steps：
1）Pre-freeze：Dianhydrogalactitol or combinations thereof ice acetic acid are made dissolving, filtration, filtrate dispenses to open containers, is placed in lyophilized cabinet, in 0.25h～5h continued down to 10 DEG C～-5 DEG C, and this temperature maintain 0.25h～5h；
2）Freeze and system balancing：After pre-freeze is terminated, continued down within the time of 0.25h～5h, lyophilized in-cabinet temperature is down to -3 DEG C～-80 DEG C, and maintains 0.25h～5h at -3 DEG C～-80 DEG C, then remain temperature-resistant and pressure in lyophilized cabinet is adjusted to 2Pa～10Pa, maintain 0.5～5h；
3）Distillation：It is passed through sterile steam or gas makes vacuum be promoted to 20Pa～150Pa, keep 0.25h～10h；
Continue to be passed through sterile steam or gas makes vacuum in 30Pa～150Pa, flaggy temperature in lyophilized cabinet is promoted to 10 DEG C～-2 DEG C for -3 DEG C～-80 DEG C by basal temperature in 0.5～5h, and is maintained at this temperature 0.5～5h；
4）Parsing：After distillation terminates, change and be passed through aseptic gas and make vacuum in 30Pa～150Pa, in the lyophilized cabinet of adjustment, flaggy temperature is 20 DEG C～40 DEG C, and maintains 0.5h～10h with this understanding；
5）Lyophilized end：After lyophilized in-cabinet temperature reaches 20 DEG C and at least two product temperatures are popped one's head in more than 20 DEG C, the vacuum in the lyophilized cabinet of adjustment to 0.1Pa～5Pa and keeps 1～10h, and end is lyophilized to be operated, and opens cabinet door, discharging.
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| CN201510452601.0A CN106389347A (en) | 2015-07-29 | 2015-07-29 | Applications of glacial acetic acid in freeze drying process of dianhydrodulcitol or composition thereof |
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Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102512466A (en) * | 2011-12-27 | 2012-06-27 | 广西梧州制药（集团）股份有限公司 | Panax notoginseng saponins freeze-dried powder injection and preparation method thereof |
| CN103923039A (en) * | 2014-01-30 | 2014-07-16 | 天津中津药业股份有限公司 | Method for preparing dianhydrogalactitol |
-
2015
- 2015-07-29 CN CN201510452601.0A patent/CN106389347A/en active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102512466A (en) * | 2011-12-27 | 2012-06-27 | 广西梧州制药（集团）股份有限公司 | Panax notoginseng saponins freeze-dried powder injection and preparation method thereof |
| CN103923039A (en) * | 2014-01-30 | 2014-07-16 | 天津中津药业股份有限公司 | Method for preparing dianhydrogalactitol |
Non-Patent Citations (1)
| Title |
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| 左建国: "有机溶剂的冷冻干燥研究", 《食品工业科技》 * |
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Application publication date: 20170215 |