CN1313476C - Injection preparation of arjimycin water soluble phosphate and its preparation method - Google Patents
Injection preparation of arjimycin water soluble phosphate and its preparation method Download PDFInfo
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- CN1313476C CN1313476C CNB03150874XA CN03150874A CN1313476C CN 1313476 C CN1313476 C CN 1313476C CN B03150874X A CNB03150874X A CN B03150874XA CN 03150874 A CN03150874 A CN 03150874A CN 1313476 C CN1313476 C CN 1313476C
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- Prior art keywords
- azythromycin
- preparation
- azithromycin
- water
- phosphoric acid
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- Expired - Lifetime
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- 238000002360 preparation method Methods 0.000 title claims abstract description 28
- 239000007924 injection Substances 0.000 title claims abstract description 25
- 238000002347 injection Methods 0.000 title claims abstract description 25
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 title claims abstract description 16
- 229910019142 PO4 Inorganic materials 0.000 title claims abstract description 15
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 title claims abstract description 15
- 239000010452 phosphate Substances 0.000 title claims abstract description 15
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 claims abstract description 25
- 229910000147 aluminium phosphate Inorganic materials 0.000 claims abstract description 12
- 239000000243 solution Substances 0.000 claims abstract description 9
- MQTOSJVFKKJCRP-HHZDEWPHSA-N Azythromycin Chemical compound O([C@@H]1[C@@H](C)C(=O)O[C@H]([C@@]([C@H](O)[C@H](C)N(C)C[C@@H](C)C[C@](C)(O)[C@@H](O[C@@H]2[C@H]([C@@H](C[C@H](C)O2)N(C)C)O)[C@@H]1C)(C)O)CC)[C@@H]1C[C@](C)(OC)[C@H](O)[C@@H](C)O1 MQTOSJVFKKJCRP-HHZDEWPHSA-N 0.000 claims description 48
- 238000006243 chemical reaction Methods 0.000 claims description 9
- 239000000843 powder Substances 0.000 claims description 8
- 239000007864 aqueous solution Substances 0.000 claims description 6
- -1 Azythromycin phosphoric acid salt Chemical class 0.000 claims description 5
- 238000009472 formulation Methods 0.000 claims description 5
- 238000000034 method Methods 0.000 claims description 5
- 239000000203 mixture Substances 0.000 claims description 5
- 239000007788 liquid Substances 0.000 claims description 4
- 239000002904 solvent Substances 0.000 claims description 4
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 3
- 239000003978 infusion fluid Substances 0.000 claims description 3
- 150000002576 ketones Chemical class 0.000 claims description 3
- 238000002156 mixing Methods 0.000 claims description 3
- 238000011146 sterile filtration Methods 0.000 claims description 3
- 239000007810 chemical reaction solvent Substances 0.000 claims description 2
- 238000001035 drying Methods 0.000 claims description 2
- 238000001291 vacuum drying Methods 0.000 claims description 2
- 150000003839 salts Chemical class 0.000 abstract description 20
- MQTOSJVFKKJCRP-BICOPXKESA-N azithromycin Chemical compound O([C@@H]1[C@@H](C)C(=O)O[C@@H]([C@@]([C@H](O)[C@@H](C)N(C)C[C@H](C)C[C@@](C)(O)[C@H](O[C@H]2[C@@H]([C@H](C[C@@H](C)O2)N(C)C)O)[C@H]1C)(C)O)CC)[C@H]1C[C@@](C)(OC)[C@@H](O)[C@H](C)O1 MQTOSJVFKKJCRP-BICOPXKESA-N 0.000 abstract description 13
- 229960004099 azithromycin Drugs 0.000 abstract description 10
- 239000003120 macrolide antibiotic agent Substances 0.000 abstract description 3
- 235000011007 phosphoric acid Nutrition 0.000 abstract 2
- 150000003016 phosphoric acids Chemical class 0.000 abstract 2
- 125000004435 hydrogen atom Chemical group [H]* 0.000 abstract 1
- 238000010521 absorption reaction Methods 0.000 description 4
- 239000002253 acid Substances 0.000 description 4
- 238000005406 washing Methods 0.000 description 4
- 239000008215 water for injection Substances 0.000 description 4
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 239000006210 lotion Substances 0.000 description 3
- 238000004519 manufacturing process Methods 0.000 description 3
- 238000003756 stirring Methods 0.000 description 3
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 2
- 102000004160 Phosphoric Monoester Hydrolases Human genes 0.000 description 2
- 108090000608 Phosphoric Monoester Hydrolases Proteins 0.000 description 2
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 2
- FKNQFGJONOIPTF-UHFFFAOYSA-N Sodium cation Chemical compound [Na+] FKNQFGJONOIPTF-UHFFFAOYSA-N 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 238000004108 freeze drying Methods 0.000 description 2
- FUZZWVXGSFPDMH-UHFFFAOYSA-N hexanoic acid Chemical compound CCCCCC(O)=O FUZZWVXGSFPDMH-UHFFFAOYSA-N 0.000 description 2
- 238000001990 intravenous administration Methods 0.000 description 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
- 238000012856 packing Methods 0.000 description 2
- 238000007911 parenteral administration Methods 0.000 description 2
- 229910052698 phosphorus Inorganic materials 0.000 description 2
- 239000011574 phosphorus Substances 0.000 description 2
- 229910001415 sodium ion Inorganic materials 0.000 description 2
- 230000000638 stimulation Effects 0.000 description 2
- UOQHWNPVNXSDDO-UHFFFAOYSA-N 3-bromoimidazo[1,2-a]pyridine-6-carbonitrile Chemical compound C1=CC(C#N)=CN2C(Br)=CN=C21 UOQHWNPVNXSDDO-UHFFFAOYSA-N 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
- WUTMHODASJRZBL-KUJJYQHYSA-N Cl.Cl.O([C@@H]1[C@@H](C)C(=O)O[C@@H]([C@@]([C@H](O)[C@@H](C)N(C)C[C@H](C)C[C@@](C)(O)[C@H](O[C@H]2[C@@H]([C@H](C[C@@H](C)O2)N(C)C)O)[C@H]1C)(C)O)CC)[C@H]1C[C@@](C)(OC)[C@@H](O)[C@H](C)O1 Chemical compound Cl.Cl.O([C@@H]1[C@@H](C)C(=O)O[C@@H]([C@@]([C@H](O)[C@@H](C)N(C)C[C@H](C)C[C@@](C)(O)[C@H](O[C@H]2[C@@H]([C@H](C[C@@H](C)O2)N(C)C)O)[C@H]1C)(C)O)CC)[C@H]1C[C@@](C)(OC)[C@@H](O)[C@H](C)O1 WUTMHODASJRZBL-KUJJYQHYSA-N 0.000 description 1
- ULGZDMOVFRHVEP-RWJQBGPGSA-N Erythromycin Chemical compound O([C@@H]1[C@@H](C)C(=O)O[C@@H]([C@@]([C@H](O)[C@@H](C)C(=O)[C@H](C)C[C@@](C)(O)[C@H](O[C@H]2[C@@H]([C@H](C[C@@H](C)O2)N(C)C)O)[C@H]1C)(C)O)CC)[C@H]1C[C@@](C)(OC)[C@@H](O)[C@H](C)O1 ULGZDMOVFRHVEP-RWJQBGPGSA-N 0.000 description 1
- 229930006677 Erythromycin A Natural products 0.000 description 1
- 206010062717 Increased upper airway secretion Diseases 0.000 description 1
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-L Phosphate ion(2-) Chemical compound OP([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-L 0.000 description 1
- 230000002159 abnormal effect Effects 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 230000000843 anti-fungal effect Effects 0.000 description 1
- 230000000845 anti-microbial effect Effects 0.000 description 1
- 229940121375 antifungal agent Drugs 0.000 description 1
- 235000003704 aspartic acid Nutrition 0.000 description 1
- 229960005261 aspartic acid Drugs 0.000 description 1
- XYOVOXDWRFGKEX-UHFFFAOYSA-N azepine Chemical compound N1C=CC=CC=C1 XYOVOXDWRFGKEX-UHFFFAOYSA-N 0.000 description 1
- OQFSQFPPLPISGP-UHFFFAOYSA-N beta-carboxyaspartic acid Natural products OC(=O)C(N)C(C(O)=O)C(O)=O OQFSQFPPLPISGP-UHFFFAOYSA-N 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 239000003610 charcoal Substances 0.000 description 1
- 229960004106 citric acid Drugs 0.000 description 1
- 235000015165 citric acid Nutrition 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-M dihydrogenphosphate Chemical compound OP(O)([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-M 0.000 description 1
- 238000007599 discharging Methods 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 229960003276 erythromycin Drugs 0.000 description 1
- 230000002349 favourable effect Effects 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 229960002989 glutamic acid Drugs 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 1
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- 210000000936 intestine Anatomy 0.000 description 1
- 239000004310 lactic acid Substances 0.000 description 1
- 235000014655 lactic acid Nutrition 0.000 description 1
- 229960000448 lactic acid Drugs 0.000 description 1
- 229940099563 lactobionic acid Drugs 0.000 description 1
- 230000014759 maintenance of location Effects 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 229940045641 monobasic sodium phosphate Drugs 0.000 description 1
- 239000006186 oral dosage form Substances 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 208000026435 phlegm Diseases 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 210000002784 stomach Anatomy 0.000 description 1
- 230000002792 vascular Effects 0.000 description 1
Landscapes
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The present invention relates to an injection preparation of the water soluble phosphate of azithromycin and a preparation method thereof, which relates to the new water soluble phosphoric acid salt of macrolide antibiotic azithromycin, an injection thereof for injecting and a preparation method thereof. The preparation method of the water soluble phosphoric acid salt of azithromycin is characterized in that the azithromycin and phosphoric acid with proper quantity are dissolved in a solution, and the mole number of H3PO4 is 1.8 to 2.5 times than that of azithromycin. Azithromycin phosphate obtained by the preparation method is prepared by the combination of azithromycin and a dihydro hydrogen group with two moles. A molecular formula is C38H72N2O12. (H2PO4). The azithromycin phosphate of the present invention has good stability to moisture. Even if the azithromycin phosphate of the present invention is placed for 2 days under the conditions of 75% of relative moisture and at the temperature of 25 DEG C, weight is just increased by approximate 3%. Appearance has no change and a dried content is unchanged. The salt is reserved for 6 month in a high-temperature closed container, and the clarity, the pH value and the appearance of the salt have no change. A content is lowered by 2%. Preparation is convenient, and technical conditions are easy to control.
Description
Technical field
Injection type of the water-soluble phosphate of Azythromycin of the present invention and preparation method thereof relates to new water-soluble phosphate and injection injection and its manufacture method of a macrolide antibiotics Azythromycin.
Background technology
Azythromycin (Azithromycin, C
38H
72N
2O
12, molecular weight 748.99) and be a kind of semisynthetic azepine fifteen-membered ring macrolide antibiotics, its structural formula is as follows:
Compare advantage such as that Azythromycin has is more stable to acid, concentration height, acting duration length, has a broad antifungal spectrum, side effect be low in body tissue with the parent stock Erythromycin A.
But it is water-soluble very little, can't directly make injection, thus usually with oral preparation for clinical use, but oral preparation bioavailability only about 40%, major part has been wasted.Oral preparation can not oral administration administration or the abnormal patient of stomach and intestine absorptive function for some, and the comparatively serious patient of some state of an illness and being not suitable for.Thereby, but the Azythromycin novel form that the exploitation injection for intravenous is used is necessary clinically.
1984, US4474768 has invented the water-soluble salt of Azythromycin---dihydrochloride first, it have identical biological activity with Zitromax, moderate pH value, can make liquid drugs injection and powder pin, be used for parenteral administration, this invention provides the preparation method of hydrochloride, but yield is on the low side, only is 54%.
Nineteen ninety-five, CN95104228 discloses the new preparation process of azithromycin dihydrochloride, and this yield is brought up to 98%, is used to produce the sterilized powder of injection but this method relates to a large amount of organic solvents and highly acid hydrogen chloride gas, as suitable difficulty.
Other water-soluble salts of Azythromycin have just been invented in the auspicious grade of nineteen ninety-five CN95106702 Shen man, also can be used as injection, these salt are that Azythromycin forms with L-glutamic acid, aspartic acid, lactic acid, citric acid, lactobionic acid, caproic acid reaction respectively, adopt lyophilize to make aseptic powder, the aqueous solution pH of these salt is all about 6, wherein the concentration of Azythromycin all can reach 250mg/ml, but the salt moisture absorption that wherein has is serious, is difficult to be applied to produce.
CN96116135 then discloses by Azythromycin and salt-SODIUM PHOSPHATE, MONOBASIC and has formed water-soluble double salt, as Azythromycin and micromolecular NaH
2PO
4After being combined into double salt, water-solublely strengthened greatly, aqueous solution pH 7-8 stimulates minimumly near human vas, and especially this salt is difficult for moisture absorption, produces more or less freely.
1998, CN98124980 also provided Azythromycin and another salt---Citric Acid sodium dihydrogen, also can form water-soluble double salt.This salt is difficult for the moisture absorption equally.But aqueous solution pH is 6-7.5.This double salt is stable better than the Azythromycin citrate.Littler to vascular stimulation, be more suitable for suitability for industrialized production.But this salt is injection not only, also can make various oral preparation.Two kinds of Azythromycin double salt that CN98124980 and CN96116135 provide all contain the sodium ion of 2.4%-4.7%, for limiting some patient that sodium ion is taken in clinically, must use cautiously.
Summary of the invention
It is more convenient, economical to the invention provides a kind of preparation method, is easy to the injection type and preparation method thereof of water-soluble phosphate of the Azythromycin of suitability for industrialized production.
The present invention is achieved in that a kind of preparation method of water-soluble phosphate of Azythromycin, it is characterized in that: the phosphoric acid of Azythromycin and appropriate amount reacts dissolving, H in solution
3PO
4Mole number should be Azythromycin 1.8-2.5 doubly.Phosphoric acid is more gentleer than sulfuric acid, acid more weak mineral acid.The biphosphate gene also is generally regarded as safe clinically, allows its sodium salt to be applied to the auxiliary material of medicine, often makes freeze-dried excipient.
Azythromycin is an alkaline compound, and pH is about about 10.Two substituted-aminos are arranged in its molecule.Thereby apparent divalence alkalescence, when phosphatase reaction, it can only react with a H in the phosphoric acid, can't generate (HPO4) with second H reaction
-2Salt.
On the such scheme basis, solvent for use is a water in the preparation method's of the water-soluble phosphate of Azythromycin the reaction system, or contains the mixing solutions of a small amount of alcohol, ketone, and pH value of aqueous solution is 5-6.
Its H among the preparation method of the water-soluble phosphate of described Azythromycin
3PO
4Mole number be preferably Azythromycin 2-2.1 doubly.To concentration of phosphoric acid, there is not strict restriction, but from the back lyophilize meter in step, should not be rare excessively.
According to the Azythromycin phosphoric acid salt of above-mentioned preparation method's gained, it is by the phosphoric acid be combined into of one mole of Azythromycin and two moles, and molecular formula is: C
38H
74N
2O
12. (H
2PO
4)
2
The phosphatic formulation of Azythromycin of the present invention comprises aqueous injection, infusion solution, powder injection.
Described Azythromycin phosphoric acid salt powder injection is formed through the sterile filtration lyophilize by the Azythromycin aqueous phosphatic.
When the phosphatase reaction of Azythromycin and 2 moles, the Azythromycin dihydrogen phosphate pH of generation is about 5.5.Through experimental observation human vas is almost had no stimulation.Be fit to intravenous administration.
HPLC shows, has Azythromycin in its aqueous solution, and this salify and dissolution process do not influence and do not destroy Azythromycin, thereby has the identical retention time and the area of Azythromycin raw material (alkali).
This salt has kept the antimicrobial characteristic of Azythromycin fully, possesses all requirements of injection, is particularly suitable for parenteral administration.
Superiority of the present invention is: this salt pair moisture is more stable.Even in the environment of 25 ℃ of relative humidity 75%, temperature, placed 2 days, only increase weight about 3%.Outward appearance is no change almost, and the content of giving money as a gift is constant.This salt was preserved 6 months in high-temperature airtight container, and clarity, pH, outward appearance be no change all, and content only descends about 2%.Easy to prepare, easy control of process conditions.
This salt not only can be made into powder injection, also can be made into aqueous injection, infusion solution and various oral dosage form.Because product solvability of the present invention is good, ought to be faster more complete than the oral preparation absorption of directly making with Azythromycin, all these formulations are applicable to the various indications of Zitromax rope fully.
The common water of solvent of reaction, or contain the mixing solutions of a small amount of alcohol, ketone.As injection, should adopt reduce phlegm and internal heat former water or water for injection.
When using water as reaction solvent, should be 2-5 times of Azythromycin, optimum is 3 times of amounts.Salifiable temperature of reaction does not have strict demand, is controlled at usually between 20-30 ℃.
During the feed liquid lyophilize, temperature should be-20 ℃ to-60 ℃, and suitable is-40 ℃.After this temperature high vacuum is taken out about 8 hours, heat up equably with 1-2 ℃ the speed of per hour raising, proceed to vacuum-drying simultaneously.Expect temperature rise to 40 ℃ the most at last.Whole drying process approximately needs 40-50 hour.
By following examples so that the present invention to be described better.But the present invention is not subjected to the restriction of following embodiment.
Embodiment
Embodiment one:
In the 100ml three-necked bottle, (961 μ that tire/mg), stir fast down drip the solution of phosphoric acid (85%) 2.7ml and 8ml water slowly, last 35 minutes and add to pour 50ml water for injection and 15g Azythromycin into.It is clear that feed liquid becomes, and stirred 30 minutes under the equality of temperature again.Filter, filter paper is washed with 3ml, and washing lotion stoste merges, and lyophilize gets Azythromycin phosphoric acid salt 18g.
Detect: moisture 0.52% pH5.7
Phosphorus content 6.3% (theoretical content 6.5%)
762 μ/mg tires
This salt favorable solubility.1ml water for injection can dissolve dose 250mg.
Embodiment two:
In the 100ml three-necked bottle, pour 2.7ml85% phosphoric acid earlier into, pour in the bottle after washing the phosphoric acid measuring container with 50ml.Slowly (947 μ that tire/mg), add back 25 ℃ and stirred 20 minutes are clear liquor, and pH5.5 filters, and filter paper is washed with 3ml to pour Azythromycin 15g under stirring into.Washing lotion stoste merges, and freeze-drying gets Azythromycin phosphoric acid salt 17.8g.
Detect: moisture 0.35% pH5.5
738 μ/ml the phosphorus content 6.41% of tiring
Embodiment three:
Add 60L water for injection in the 100L reactor, stir and pour Azythromycin 22.5kg, 20 ℃ of interior temperature down slowly into, slowly drip the solution of 4L phosphoric acid and 10L water, last 30 minutes, molten entirely, survey pH5.43, add carbon injection 0.2kg, 20 ℃ were stirred 30 minutes, filtered, and the charcoal cake is washed for 2 times with 5L moisture, the merging of washing lotion stoste enters sterilisable chamber, the freeze-drying deep bid of packing into after 0.22 μ Sterile Filtration.All be chilled to-40 ℃ after the cartonnings and vacuumized dry 8 hours, took out 18 hours per hour to heat up 1 ℃ again, took out 20 hours per hour to rise 2 ℃, will expect that at last temperature rise to 40 ℃ took out 4 hours, discharging is sieved, packing, common finished product 26.4kg.
Detect: look level＜No. 1 clarity＜0.5 of yellow
Water-content 0.47% pH value of solution 5.53
752 μ/mg specific volume 2.6ml/g tires
Claims (7)
1. the preparation method of the water-soluble phosphate of an Azythromycin, it is characterized in that: the phosphoric acid of Azythromycin and appropriate amount reacts dissolving, H in solution
3PO
4Mole number should be Azythromycin 1.8-2.5 doubly.
2. the preparation method of the water-soluble phosphate of Azythromycin according to claim 1, it is characterized in that: solvent for use is a water in the reaction, or contains the mixing solutions of a small amount of alcohol, ketone, its pH value of aqueous solution is 5-6.
3. the preparation method of the water-soluble phosphate of Azythromycin according to claim 1 is characterized in that: H
3PO
4Mole number should be Azythromycin 2-2.1 doubly.
4. the Azythromycin phosphoric acid salt of preparation method's gained according to claim 1 and 2 is characterized in that: by the phosphoric acid be combined into of one mole of Azythromycin and two moles, molecular formula is: C
38H
74N
2O
12(H
2PO
4)
2
5. the phosphatic formulation of Azythromycin that preparation method according to claim 3 obtains is characterized in that: comprise aqueous injection, infusion solution, powder injection.
6. the phosphatic formulation of Azythromycin according to claim 5, it is characterized in that: described powder injection is formed through the sterile filtration lyophilize by the Azythromycin aqueous phosphatic.
7. the phosphatic formulation of Azythromycin according to claim 6, it is characterized in that making by the following method: when using water as reaction solvent, quantity of solvent is 2-5 a times of Azythromycin, salifiable temperature of reaction is controlled between 20-30 ℃, during to the feed liquid lyophilize, temperature is between-20 ℃ to-60 ℃, after this temperature high vacuum is taken out about 8 hours, 1-2 ℃ speed evenly heats up per hour to raise, proceed to vacuum-drying simultaneously, expect temperature rise to 40 ℃ the most at last, whole drying process needs 40-50 hour.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB03150874XA CN1313476C (en) | 2003-09-09 | 2003-09-09 | Injection preparation of arjimycin water soluble phosphate and its preparation method |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB03150874XA CN1313476C (en) | 2003-09-09 | 2003-09-09 | Injection preparation of arjimycin water soluble phosphate and its preparation method |
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| Publication Number | Publication Date |
|---|---|
| CN1493579A CN1493579A (en) | 2004-05-05 |
| CN1313476C true CN1313476C (en) | 2007-05-02 |
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Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3276956A (en) * | 1963-05-31 | 1966-10-04 | Abbott Lab | Treating infections in poultry caused by pleuropneumoniia-like organisms with erythromycin phosphate |
| US4474768A (en) * | 1982-07-19 | 1984-10-02 | Pfizer Inc. | N-Methyl 11-aza-10-deoxo-10-dihydro-erytromycin A, intermediates therefor |
| CN1123279A (en) * | 1995-06-15 | 1996-05-29 | 沈家祥 | Azithmycin water-soluble salt, injection thereof and their usage |
| CN1157824A (en) * | 1996-12-28 | 1997-08-27 | 山东省医药工业研究所 | Azrinomycin dihydric phosphate complex salt and its preparation |
| RU2190410C1 (en) * | 2001-06-18 | 2002-10-10 | Акционерное Курганское общество медицинских препаратов и изделий "Синтез" | Method of injection form of erythromycin phosphate preparing |
| CN1096468C (en) * | 1998-11-27 | 2002-12-18 | 何广卫 | Adriamycin polybasic acid sodium salt complex salt |
-
2003
- 2003-09-09 CN CNB03150874XA patent/CN1313476C/en not_active Expired - Lifetime
Patent Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3276956A (en) * | 1963-05-31 | 1966-10-04 | Abbott Lab | Treating infections in poultry caused by pleuropneumoniia-like organisms with erythromycin phosphate |
| US4474768A (en) * | 1982-07-19 | 1984-10-02 | Pfizer Inc. | N-Methyl 11-aza-10-deoxo-10-dihydro-erytromycin A, intermediates therefor |
| CN1123279A (en) * | 1995-06-15 | 1996-05-29 | 沈家祥 | Azithmycin water-soluble salt, injection thereof and their usage |
| CN1157824A (en) * | 1996-12-28 | 1997-08-27 | 山东省医药工业研究所 | Azrinomycin dihydric phosphate complex salt and its preparation |
| CN1096468C (en) * | 1998-11-27 | 2002-12-18 | 何广卫 | Adriamycin polybasic acid sodium salt complex salt |
| RU2190410C1 (en) * | 2001-06-18 | 2002-10-10 | Акционерное Курганское общество медицинских препаратов и изделий "Синтез" | Method of injection form of erythromycin phosphate preparing |
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