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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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 |
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| CN1615867A true CN1615867A (en) | 2005-05-18 |
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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 (7)
| 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 |
-
2004
- 2004-10-22 CN CN 200410083899 patent/CN1615867A/en active Pending
Cited By (10)
| 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 |
| 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 |
| US10898480B1 (en) | 2019-07-09 | 2021-01-26 | Orexo Ab | Pharmaceutical composition for nasal delivery |
| US11883392B2 (en) | 2019-07-09 | 2024-01-30 | 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 |
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