CN1615867A - Naloxone hydrchloride freeze-dried powder preparation for injection - Google Patents
Naloxone hydrchloride freeze-dried powder preparation for injection Download PDFInfo
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- CN1615867A CN1615867A CN 200410083899 CN200410083899A CN1615867A CN 1615867 A CN1615867 A CN 1615867A CN 200410083899 CN200410083899 CN 200410083899 CN 200410083899 A CN200410083899 A CN 200410083899A CN 1615867 A CN1615867 A CN 1615867A
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- naloxone
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- mannitol
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- 238000002360 preparation method Methods 0.000 title claims abstract description 55
- 239000000843 powder Substances 0.000 title claims abstract description 25
- 229960004127 naloxone Drugs 0.000 title claims description 26
- 238000002347 injection Methods 0.000 title abstract description 11
- 239000007924 injection Substances 0.000 title abstract description 11
- UZHSEJADLWPNLE-GRGSLBFTSA-N naloxone Chemical compound O=C([C@@H]1O2)CC[C@@]3(O)[C@H]4CC5=CC=C(O)C2=C5[C@@]13CCN4CC=C UZHSEJADLWPNLE-GRGSLBFTSA-N 0.000 title 1
- RGPDIGOSVORSAK-STHHAXOLSA-N naloxone hydrochloride Chemical compound Cl.O=C([C@@H]1O2)CC[C@@]3(O)[C@H]4CC5=CC=C(O)C2=C5[C@@]13CCN4CC=C RGPDIGOSVORSAK-STHHAXOLSA-N 0.000 claims abstract description 62
- 229960005250 naloxone hydrochloride Drugs 0.000 claims abstract description 37
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 claims abstract description 25
- 229930195725 Mannitol Natural products 0.000 claims abstract description 25
- 239000000594 mannitol Substances 0.000 claims abstract description 25
- 235000010355 mannitol Nutrition 0.000 claims abstract description 25
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims abstract description 6
- 229920002307 Dextran Polymers 0.000 claims abstract description 3
- 229930091371 Fructose Natural products 0.000 claims abstract description 3
- RFSUNEUAIZKAJO-ARQDHWQXSA-N Fructose Chemical compound OC[C@H]1O[C@](O)(CO)[C@@H](O)[C@@H]1O RFSUNEUAIZKAJO-ARQDHWQXSA-N 0.000 claims abstract description 3
- 239000005715 Fructose Substances 0.000 claims abstract description 3
- 239000011780 sodium chloride Substances 0.000 claims abstract description 3
- 239000003937 drug carrier Substances 0.000 claims description 20
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 claims description 11
- 239000008103 glucose Substances 0.000 claims description 11
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 8
- 238000004108 freeze drying Methods 0.000 claims description 8
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 claims description 7
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 claims description 2
- 239000007864 aqueous solution Substances 0.000 claims description 2
- 238000000034 method Methods 0.000 claims description 2
- 239000000600 sorbitol Substances 0.000 claims description 2
- 238000003756 stirring Methods 0.000 claims description 2
- 239000003814 drug Substances 0.000 abstract description 5
- MEIRRNXMZYDVDW-MQQKCMAXSA-N (2E,4E)-2,4-hexadien-1-ol Chemical compound C\C=C\C=C\CO MEIRRNXMZYDVDW-MQQKCMAXSA-N 0.000 abstract 1
- 229920000858 Cyclodextrin Polymers 0.000 abstract 1
- 239000001116 FEMA 4028 Substances 0.000 abstract 1
- WHGYBXFWUBPSRW-FOUAGVGXSA-N beta-cyclodextrin Chemical compound OC[C@H]([C@H]([C@@H]([C@H]1O)O)O[C@H]2O[C@@H]([C@@H](O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O3)[C@H](O)[C@H]2O)CO)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@@H]3O[C@@H]1CO WHGYBXFWUBPSRW-FOUAGVGXSA-N 0.000 abstract 1
- 235000011175 beta-cyclodextrine Nutrition 0.000 abstract 1
- 229960004853 betadex Drugs 0.000 abstract 1
- -1 glucol Chemical compound 0.000 abstract 1
- FZWBNHMXJMCXLU-BLAUPYHCSA-N isomaltotriose Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1OC[C@@H]1[C@@H](O)[C@H](O)[C@@H](O)[C@@H](OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C=O)O1 FZWBNHMXJMCXLU-BLAUPYHCSA-N 0.000 abstract 1
- 238000001035 drying Methods 0.000 description 12
- 238000010438 heat treatment Methods 0.000 description 12
- 238000003556 assay Methods 0.000 description 11
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 10
- JGSARLDLIJGVTE-UHFFFAOYSA-N 3,3-dimethyl-7-oxo-6-[(2-phenylacetyl)amino]-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid Chemical compound O=C1N2C(C(O)=O)C(C)(C)SC2C1NC(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-UHFFFAOYSA-N 0.000 description 8
- 210000004907 gland Anatomy 0.000 description 6
- 239000012528 membrane Substances 0.000 description 6
- 238000012856 packing Methods 0.000 description 6
- 238000000859 sublimation Methods 0.000 description 6
- 230000008022 sublimation Effects 0.000 description 6
- 239000008215 water for injection Substances 0.000 description 6
- 238000010255 intramuscular injection Methods 0.000 description 4
- 239000007927 intramuscular injection Substances 0.000 description 4
- 210000004204 blood vessel Anatomy 0.000 description 3
- 239000003795 chemical substances by application Substances 0.000 description 3
- 229940079593 drug Drugs 0.000 description 3
- 238000010253 intravenous injection Methods 0.000 description 3
- 210000004877 mucosa Anatomy 0.000 description 3
- 210000003205 muscle Anatomy 0.000 description 3
- 210000003491 skin Anatomy 0.000 description 3
- 239000000470 constituent Substances 0.000 description 2
- 150000004683 dihydrates Chemical class 0.000 description 2
- 230000007794 irritation Effects 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 229940124636 opioid drug Drugs 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 208000007848 Alcoholism Diseases 0.000 description 1
- 206010002091 Anaesthesia Diseases 0.000 description 1
- 239000004593 Epoxy Substances 0.000 description 1
- 102000003840 Opioid Receptors Human genes 0.000 description 1
- 108090000137 Opioid Receptors Proteins 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 201000007930 alcohol dependence Diseases 0.000 description 1
- 230000037005 anaesthesia Effects 0.000 description 1
- 230000003042 antagnostic effect Effects 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- NSNHWTBQMQIDCF-UHFFFAOYSA-N dihydrate;hydrochloride Chemical compound O.O.Cl NSNHWTBQMQIDCF-UHFFFAOYSA-N 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 230000029058 respiratory gaseous exchange Effects 0.000 description 1
- 239000008354 sodium chloride injection Substances 0.000 description 1
- 238000013112 stability test Methods 0.000 description 1
- 239000008227 sterile water for injection Substances 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 210000003462 vein Anatomy 0.000 description 1
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
Abstract
The freeze dried naloxone hydrochloride powder for injection consists of naloxone hydrochloride in effective medicine amount and proper amount of medicinal carrier. The naloxone hydrochloride content is 0.08-70.59 wt% or 0.1-12 mg; and the medicinal carrier may be one or several of mannitol, glucol, sodium chloride, beta-cyclodextrin, dextran, fructose, sorbic alcohol, etc., is preferably mannitol and glucol and has the ratio in the preparation of 29.41-99.92 wt%.
Description
Technical field:
The present invention relates to the naloxone hydrchloride freeze-dried powder preparation of a kind of pharmaceutical preparation, particularly injection, said preparation contains the naloxone hydrochloride for the treatment of effective dose and an amount of pharmaceutical carrier.
Background technology:
Naloxone hydrochloride (chemistry 17-pi-allyl-4 by name, 5a-epoxy radicals-3,14-dihydroxy morphinan-6-ones hydrochloride dihydrate (please determine whether naloxone hydrochloride has only its dihydrate to can be used for pharmacy, if the hydrate of its non-hydrate or other water content also can be used as medicine, please describe in detail at this, illustrate that promptly naloxone hydrochloride can have various ways, naloxone hydrochloride of the present invention comprises the naloxone hydrochloride of these form of ownerships, but most preferably above-mentioned dihydrate), be the opiate receptor antagonistic, be used for the respiration inhibition due to the opioid drug combined anesthesia operation back, and waken patient, it is excessive to be used for opioid drug, is used for acute alcoholism.
The naloxone hydrochloride injection that gone on the market is little liquid drugs injection, and its less stable is unfavorable for long term storage.The stability test result shows that the commercially available prod is after dispatching from the factory 1 year, and pH value is on the rise, and active constituent content descends, and related substance slightly increases.And the pH value of commercially available naloxone hydrochloride injection is 3.0-4.0, and blood vessel, skin, mucosa and muscle irritation to the patient when intramuscular injection or intravenous injection are big, and patient tolerability is poor.For improving product stability, increase patient's toleration, we have developed the naloxone hydrochloride freeze-dried powder, and specification is defined as: 0.2mg, 0.4mg, 1mg, 2mg, 4mg, 8mg.
Application number is that the Chinese patent of CN03107128.7 has been described a kind of naloxone freeze-dried powder, and said preparation is to be raw material with the naloxone, adds the pH regulator agent in preparation, and obtaining pH value is the naloxone powder injection formulation of 3.0-4.5.The crude drug that said preparation uses is naloxone, and naloxone is insoluble or almost insoluble in water, and preparation technology is difficult to carry out; And the pH value of said preparation is 3.0-4.5, and acidity is stronger, and when carrying out intramuscular injection or intravenous injection in the clinical practice, big to patient's blood vessel, skin, mucosa and muscle irritation, patient tolerability is poor, is difficult to realize the suitability for industrialized production of product.
Summary of the invention:
The object of the invention provides a kind of steady quality, be convenient to transportation and store and can rapid dissolved naloxone hydrchloride freeze-dried powder preparation, except that containing naloxone hydrochloride as the effective ingredient, also contains an amount of pharmaceutical carrier in the said preparation.
Naloxone hydrchloride freeze-dried powder preparation of the present invention is made up of naloxone hydrochloride for the treatment of effective dose and an amount of pharmaceutical carrier basically.
Naloxone hydrchloride freeze-dried powder preparation of the present invention, the content of hydrochloric acid naloxone in preparation wherein, by weight, can be 0.08%-70.59%, be preferably 0.20%-44.44%, more preferably 0.5%-21.05% most preferably is 0.66%-16.67%.
Naloxone hydrchloride freeze-dried powder preparation of the present invention, the pharmaceutical carrier that is contained is not particularly limited, so long as the carrier that can be used in the injection preparation is just passable.For example can be selected from mannitol, glucose, sodium chloride, beta-schardinger dextrin-, dextran, fructose, the sorbitol etc. one or more, be preferably mannitol and/or glucose.The content of pharmaceutical carrier also is not particularly limited, and can at random use pharmaceutical carrier in the scope of harmless effect of the present invention.The content of pharmaceutical carrier in preparation can be 29.41%-99.92% by weight, is preferably 55.56%-99.80%, and more preferably 78.95%-99.50% most preferably is 83.33%-99.34%.
Because lyophilized injectable powder normally is divided in the cillin bottle, with the unit dosage form administration, so naloxone hydrchloride freeze-dried powder preparation of the present invention, per unit dosage, be that to contain naloxone hydrochloride in every injection can be 0.1-12mg, pharmaceutical carrier for example mannitol or glucose can be 5-120mg.
Naloxone hydrchloride freeze-dried powder preparation of the present invention preferably, contains the 0.2-8mg naloxone hydrochloride in the preparation of per unit dosage; More preferably, contain 0.2mg, 0.4mg, 1mg, 2mg, 4mg, 8mg naloxone hydrochloride in the preparation of per unit dosage; Most preferably, contain 0.4mg, 1mg, 2mg, 4mg naloxone hydrochloride in the preparation of the present invention.
Naloxone hydrchloride freeze-dried powder preparation of the present invention preferably, contains pharmaceutical carrier for example mannitol or glucose 10-100mg in the preparation of per unit dosage; More preferably, contain pharmaceutical carrier for example mannitol or glucose 15-80mg in the preparation of per unit dosage; Most preferably, contain pharmaceutical carrier for example mannitol or glucose 20-60mg in the preparation of the present invention.
Naloxone hydrchloride freeze-dried powder preparation of the present invention also contains small amount of moisture sometimes, but small amount of moisture does not influence the performance and the beneficial effect of product of the present invention, moisture is in the scope of the freeze-dried powder permission of routine, and for example moisture is 0～6%.
Naloxone hydrchloride freeze-dried powder preparation of the present invention, pH value are 5.0-7.0.
Naloxone hydrchloride freeze-dried powder preparation of the present invention, its preparation method are that naloxone hydrochloride is added certain density pharmaceutical carrier for example in the aqueous solution of mannitol or glucose, and stirring and dissolving is filtered the back fill, and lyophilization makes preparation of the present invention.
Its clinical administration method of naloxone hydrchloride freeze-dried powder preparation of the present invention is: face with before adding sterilized water for injection dissolving back intramuscular injection or adding 5% glucose, 0.9% sodium chloride injection dissolving posterior vein injection or intravenous drip.
Naloxone hydrchloride freeze-dried powder preparation of the present invention, employed crude drug are naloxone hydrochloride, and its dissolubility in water is good, so preparation is simple for this product.
Naloxone hydrchloride freeze-dried powder preparation of the present invention does not add pH regulator agent such as hydrochloric acid, the products obtained therefrom pH value is 5.0-7.0, approach neutrality, blood vessel, skin, mucosa and muscle to the patient when carrying out intramuscular injection or intravenous injection in clinical use almost do not stimulate, and have improved patient's toleration greatly.In addition, in naloxone hydrchloride freeze-dried powder preparation preparation process of the present invention, do not add pH regulator agent such as hydrochloric acid not only reduced in preparation, introduce other impurity may, and simplified technology, reduced production cost.
Naloxone hydrchloride freeze-dried powder preparation reasonable recipe of the present invention, technology is simple, and product is loose porous, and solubility is good, good stability.Factors influencing under high temperature, high humidity, high light condition 10 days and 40 ℃ of accelerated tests 6 months, sample appearance character, pH, active constituent content and related substance etc. have no significant change.
Naloxone hydrochloride is a known compound, and its standard is recorded in " Chinese pharmacopoeia (version was two ones in 2000) can oneself prepare or commercially available obtaining.
The specific embodiment:
Further specify the present invention by the following examples, but these embodiment do not limit the present invention in any way.
Embodiment 1
Prescription:
Naloxone hydrochloride 0.2g
Mannitol 10g
Technology: 1. get 1000ml water for injection and put in the dosing cylinder, add the mannitol of prescription full dose, be stirred to dissolving; 2. add the naloxone hydrochloride of recipe quantity, be stirred to dissolving; The microporous filter membrane fine straining of reuse 0.22 μ m is to clear and bright; 3. embedding (fill 1ml liquid in the cillin bottle of 2ml volume) in cillin bottle; 4. lyophilization (pre-freeze, make temperature drop to-40 ℃, the heating rate with 0.15 ℃ of per minute after two hours rises to temperature-5 ℃, and sublimation drying is 10 hours under this temperature, heating rate with 0.4 ℃ of per minute rises to 40 ℃ with temperature again, and drying is 7～10 hours under this temperature); 5. gland is labelled, and packing gets product after the assay was approved.PH value: get 10 of this product, every adds water 1ml dissolving back merging, measures (two appendix VI of Chinese Pharmacopoeia version in 2000 H) in accordance with the law, and pH value is 6.06.
Embodiment 2
Prescription:
Naloxone hydrochloride 0.4g
Mannitol 20g
Technology: 1. get 1000ml water for injection and put in the dosing cylinder, add the mannitol of prescription full dose, be stirred to dissolving; 2. add the naloxone hydrochloride of recipe quantity, be stirred to dissolving; The microporous filter membrane fine straining of reuse 0.22 μ m is to clear and bright; 3. embedding (with embodiment 1) in cillin bottle; 4. lyophilization (pre-freeze, make temperature drop to-40 ℃, the heating rate with 0.15 ℃ of per minute after two hours rises to temperature-5 ℃, and sublimation drying is 10 hours under this temperature, heating rate with 0.4 ℃ of per minute rises to 40 ℃ with temperature again, and drying is 7～10 hours under this temperature); 5. gland is labelled, and packing gets product after the assay was approved.
PH value: assay method is with embodiment 1, and pH value is 6.06.。
Embodiment 3
Prescription:
Naloxone hydrochloride 1g
Mannitol 30g
Technology: 1. get 1000ml water for injection and put in the dosing cylinder, add the mannitol of prescription full dose, be stirred to dissolving; 2. add the naloxone hydrochloride of recipe quantity, be stirred to dissolving; The microporous filter membrane fine straining of reuse 0.22 μ m is to clear and bright; 3. embedding (with embodiment 1) in cillin bottle; 4. lyophilization (pre-freeze, make temperature drop to-40 ℃, the heating rate with 0.15 ℃ of per minute after two hours rises to temperature-5 ℃, and sublimation drying is 10 hours under this temperature, heating rate with 0.4 ℃ of per minute rises to 40 ℃ with temperature again, and drying is 7～10 hours under this temperature); 5. gland is labelled, and packing gets product after the assay was approved.
PH value: assay method is with embodiment 1, and pH value is 5.85.
Embodiment 4
Prescription:
Naloxone hydrochloride 2g
Mannitol 50g
Technology: 1. get 1000ml water for injection and put in the dosing cylinder, add the mannitol of prescription full dose, be stirred to dissolving; 2. add the naloxone hydrochloride of recipe quantity, be stirred to dissolving; The microporous filter membrane fine straining of reuse 0.22 μ m is to clear and bright; 3. embedding (with embodiment 1) in cillin bottle; 4. lyophilization (pre-freeze, make temperature drop to-40 ℃, the heating rate with 0.15 ℃ of per minute after two hours rises to temperature-5 ℃, and sublimation drying is 10 hours under this temperature, heating rate with 0.4 ℃ of per minute rises to 40 ℃ with temperature again, and drying is 7～10 hours under this temperature); 5. gland is labelled, and packing gets product after the assay was approved.
PH value: assay method is with embodiment 1, and pH value is 6.18.
Embodiment 5
Prescription:
Naloxone hydrochloride 4g
Mannitol 80g
Technology: 1. get 1000ml water for injection and put in the dosing cylinder, add the mannitol of prescription full dose, be stirred to dissolving; 2. add the naloxone hydrochloride of recipe quantity, be stirred to dissolving; The microporous filter membrane fine straining of reuse 0.22 μ m is to clear and bright; 3. embedding (with embodiment 1) in cillin bottle; 4. lyophilization (pre-freeze, make temperature drop to-40 ℃, the heating rate with 0.15 ℃ of per minute after two hours rises to temperature-5 ℃, and sublimation drying is 10 hours under this temperature, heating rate with 0.4 ℃ of per minute rises to 40 ℃ with temperature again, and drying is 7～10 hours under this temperature); 5. gland is labelled, and packing gets product after the assay was approved.
PH value: assay method is with embodiment 1, and pH value is 6.25.
Embodiment 6
Prescription:
Naloxone hydrochloride 8g
Mannitol 100g
Technology: 1. get 1000ml water for injection and put in the dosing cylinder, add the mannitol of prescription full dose, be stirred to dissolving; 2. add the naloxone hydrochloride of recipe quantity, be stirred to dissolving; The microporous filter membrane fine straining of reuse 0.22 μ m is to clear and bright; 3. embedding (with embodiment 1) in cillin bottle; 4. lyophilization (pre-freeze, make temperature drop to-40 ℃, the heating rate with 0.15 ℃ of per minute after two hours rises to temperature-5 ℃, and sublimation drying is 10 hours under this temperature, heating rate with 0.4 ℃ of per minute rises to 40 ℃ with temperature again, and drying is 7～10 hours under this temperature); 5. gland is labelled, and packing gets product after the assay was approved.
PH value: assay method is with embodiment 1, and pH value is 6.10.
Claims (10)
1, a kind of naloxone hydrchloride freeze-dried powder preparation is characterized in that containing naloxone hydrochloride and pharmaceutical carrier.
2, according to the preparation of claim 1, wherein the content of hydrochloric acid naloxone is 0.08%-70.59% by weight percentage in the preparation, and the content of pharmaceutical carrier is 29.41%-99.92% by weight.
3, according to the preparation of claim 1, wherein pharmaceutical carrier is selected from one or more in mannitol, glucose, sodium chloride, beta-schardinger dextrin-, dextran, fructose, the sorbitol.
4, according to the preparation of claim 3, wherein pharmaceutical carrier is selected from mannitol and/or glucose.
5, according to the preparation of claim 4, wherein pharmaceutical carrier is a mannitol.
6, according to the preparation of one of claim 1-5, wherein contain naloxone hydrochloride 0.1-12mg in the preparation of per unit dosage, pharmaceutical carrier 5-120mg.
7, according to the preparation of claim 6, wherein contain naloxone hydrochloride 0.2mg in the per unit preparation, 0.4mg, 1mg, 2mg, 4mg or 8mg.
8, the preparation of one of claim 1-7 meaning, wherein the pH value of preparation is 5.0-7.0.
9, the preparation method of one of any preparation of claim 1-8 is characterized in that this method comprises naloxone hydrochloride is added in the aqueous solution of certain density pharmaceutical carrier, and stirring and dissolving is filtered the back fill, lyophilization.
10, according to the preparation method of claim 9, wherein pharmaceutical carrier is selected from mannitol and/or glucose.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 200410083899 CN1615867A (en) | 2004-10-22 | 2004-10-22 | Naloxone hydrchloride freeze-dried powder preparation for injection |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 200410083899 CN1615867A (en) | 2004-10-22 | 2004-10-22 | Naloxone hydrchloride freeze-dried powder preparation for injection |
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| Publication Number | Publication Date |
|---|---|
| CN1615867A true CN1615867A (en) | 2005-05-18 |
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| Application Number | Title | Priority Date | Filing Date |
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| CN 200410083899 Pending CN1615867A (en) | 2004-10-22 | 2004-10-22 | Naloxone hydrchloride freeze-dried powder preparation for injection |
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Cited By (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102166198A (en) * | 2011-03-30 | 2011-08-31 | 重庆健能医药开发有限公司 | Stable naloxone hydrochloride freeze-dry preparation and preparation method thereof |
| CN102274196A (en) * | 2011-07-19 | 2011-12-14 | 浙江浙北药业有限公司 | Naloxone hydrochloride freeze-dried powder injection and preparation method thereof |
| CN103304570A (en) * | 2013-07-12 | 2013-09-18 | 四川省惠达药业有限公司 | Naloxone hydrochloride compound as well as preparation method and pharmaceutical composition of naloxone hydrochloride compound |
| US10653690B1 (en) | 2019-07-09 | 2020-05-19 | Orexo Ab | Pharmaceutical composition for nasal delivery |
| US10729687B1 (en) | 2019-07-09 | 2020-08-04 | Orexo Ab | Pharmaceutical composition for nasal delivery |
| US11737980B2 (en) | 2020-05-18 | 2023-08-29 | Orexo Ab | Pharmaceutical composition for drug delivery |
| US11957647B2 (en) | 2021-11-25 | 2024-04-16 | Orexo Ab | Pharmaceutical composition comprising adrenaline |
| US12303472B2 (en) | 2021-11-25 | 2025-05-20 | Orexo Ab | Pharmaceutical device for use in intranasal administration |
-
2004
- 2004-10-22 CN CN 200410083899 patent/CN1615867A/en active Pending
Cited By (14)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102166198A (en) * | 2011-03-30 | 2011-08-31 | 重庆健能医药开发有限公司 | Stable naloxone hydrochloride freeze-dry preparation and preparation method thereof |
| CN102274196A (en) * | 2011-07-19 | 2011-12-14 | 浙江浙北药业有限公司 | Naloxone hydrochloride freeze-dried powder injection and preparation method thereof |
| CN102274196B (en) * | 2011-07-19 | 2013-04-10 | 浙江浙北药业有限公司 | Naloxone hydrochloride freeze-dried powder injection and preparation method thereof |
| CN103304570A (en) * | 2013-07-12 | 2013-09-18 | 四川省惠达药业有限公司 | Naloxone hydrochloride compound as well as preparation method and pharmaceutical composition of naloxone hydrochloride compound |
| US10898480B1 (en) | 2019-07-09 | 2021-01-26 | Orexo Ab | Pharmaceutical composition for nasal delivery |
| US10729687B1 (en) | 2019-07-09 | 2020-08-04 | Orexo Ab | Pharmaceutical composition for nasal delivery |
| US10653690B1 (en) | 2019-07-09 | 2020-05-19 | Orexo Ab | Pharmaceutical composition for nasal delivery |
| US11883392B2 (en) | 2019-07-09 | 2024-01-30 | Orexo Ab | Pharmaceutical composition for nasal delivery |
| US12268684B2 (en) | 2019-07-09 | 2025-04-08 | Orexo Ab | Pharmaceutical composition for nasal delivery |
| US11737980B2 (en) | 2020-05-18 | 2023-08-29 | Orexo Ab | Pharmaceutical composition for drug delivery |
| US12357573B2 (en) | 2020-05-18 | 2025-07-15 | Orexo Ab | Pharmaceutical composition for drug delivery |
| US11957647B2 (en) | 2021-11-25 | 2024-04-16 | Orexo Ab | Pharmaceutical composition comprising adrenaline |
| US12303472B2 (en) | 2021-11-25 | 2025-05-20 | Orexo Ab | Pharmaceutical device for use in intranasal administration |
| US12472154B2 (en) | 2021-11-25 | 2025-11-18 | Orexo Ab | Pharmaceutical composition comprising adrenaline |
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