You’re using a public version of DrugPatentWatch with 5 free searches available | Register to unlock more free searches. CREATE FREE ACCOUNT

Last Updated: March 29, 2024

Claims for Patent: 4,308,264


✉ Email this page to a colleague

« Back to Dashboard


Summary for Patent: 4,308,264
Title: Stabilized, dilute aqueous preparation of 1.alpha.,25-dihydroxycholecalciferol for neonatal administration
Abstract:1.alpha.,25-Dihydroxycholecalciferol, also known as 1.alpha.,25-dihydroxyvitamin D.sub.3, calcitriol or 1.alpha.,25(OH).sub.2 D.sub.3, occurs naturally in man as the active form of cholecalciferol or vitamin D.sub.3. The natural supply of vitamin D.sub.3 depends on the conversion of 7-dehydrocholesterol to vitamin D.sub.3 in the skin by ultraviolet light. Vitamin D.sub.3 is then converted to calcitriol in a two-step process in the liver and kidney before its acts on its target tissue.
Inventor(s): Conway; Nancy M. (Mundelein, IL), Krimen; Lewis I. (Lake Bluff, IL)
Assignee: Abbott Laboratories (North Chicago, IL)
Application Number:06/228,870
Patent Claims: 1. A pharmaceutical dosage form of 1.alpha.,25-dihydroxycholecalciferol comprising a therapeutically effective amount of 1.alpha.,25-dihydroxycholecalciferol to prevent hypocalcemia solubilized in water with a nonionic surfactant and stabilized with a combination of a metal ascorbate and a chelating agent in the presence of an inert atmosphere at pH 6.4 to 7.8.

2. The pharmaceutical dosage form of claim 1 wherein an excess of said metal ascorbate is present to stabilize said 1.alpha.,25-dihydroxycholecalciferol.

3. The pharmaceutical dosage form of claim 1 wherein said 1.alpha.,25-dihydroxycholecalciferol is solubilized in water with from 400 to 80,000 parts by weight of a nonionic surfactant, and stabilized with a combination of from 100 to 10,000 parts by weight of a metal ascorbate and from 100 to 10,000 parts by weight of a chelating agent at pH 7.0 to 7.8 in the presence of an inert atmosphere.

4. The pharmaceutical dosage form of claim 3 wherein said metal ascorbate is an alkali or alkaline earth metal ascorbate.

5. The pharmaceutical dosage form of claims 1, 2, 3 or 4 wherein said pH is 7.0 to 7.5.

6. The pharmaceutical dosage form of claims 1, 2, 3 or 4 wherein said pH is 7.0 to 7.3.

7. The pharmaceutical dosage form of claim 1 wherein 1.alpha.,25-dihydroxycholecalciferol solubilized in water with 4,000 parts by weight of a nonionic surfactant, and stabilized by a combination of 10,000 parts by weight of a metal ascorbate, 1,000 parts by weight of a chelating agent and an inert atmosphere at pH 7.0 to 7.8.

8. The product of claim 7 wherein said metal ascorbate is an alkaline earth or alkali metal ascorbate.

9. The product of claim 7 wherein said metal ascorbate is sodium ascorbate.

10. The product of claims 7, 8 or 9 wherein said chelating agent is sodium edetate.

11. The product of claims 7, 8, 9 or 10 wherein said inert atmosphere is nitrogen.

12. A pharmaceutical composition which is a dilute, stable, aqueous solution of 1.alpha.,25-dihydroxycholecalciferol comprising 1 part by weight of said 1.alpha.,25-dihydroxycholecalciferol, 10,000 parts by weight of sodium ascorbate, 4,000 parts by weight of a polysorbate 20 nonionic surfactant, 1,000 parts by weight of disodium edetate, 1,500 parts by weight of sodium chloride, 7,600 parts by weight of sodium phosphate dibasic, 1,840 parts by weight of sodium phosphate monobasic, water q.s. and nitrogen q.s. and having a pH of between 6.4 and 7.8.

13. The solution of claim 12 wherein said pH is between 7.0 to 7.8.

14. The solution of claim 12 wherein said pH is between 7.0 and 7.5.

15. The solution of claim 12 wherein said solution is isotonic.

16. A process for preparing a stable, dilute, aqueous solution of 1.alpha.,25-dihydroxycholecalciferol comprising the steps of: preparing a concentrate of said 1.alpha.,25-dihydroxycholecalciferol and a nonionic surfactant under an inert atmosphere; preparing an aqueous solution of a metal ascorbate, a chelating agent and a buffering agent under an inert atmosphere, said solution having a pH of from 7.0 to 7.8; and, adding said concentrate to said aqueous, buffered solution, with stirring under an inert atmosphere.

17. The process of claim 16 wherein said aqueous solution additionally comprises sodium chloride.

18. The process of claim 16 or 17 wherein said metal ascorbate is an alkali metal or alkaline earth metal ascorbate and said ascorbate is present in an amount of from 1,000 to 15,000 parts by weight per part of said 1.alpha.,25-dihydroxycholecalciferol.

19. The process of claim 16, 17 or 18 wherein said nonionic surfactant is heated to a temperature of from about 50.degree. to 75.degree. C. prior to the addition of said 1.alpha.,25-dihydroxycholecalciferol, and said solution is allowed to cool prior to the addition thereof to said aqueous solution.

20. The process of claim 16, 17, 18 or 19 wherein the water used to prepare said aqueous solution is heated to a temperature of between 85.degree. to 100.degree. C. and cooled to a temperature of from about 20.degree. C. to 50.degree. C. prior to the addition of said metal ascorbate, said chelating agent and said buffering agents.

Make Better Decisions: Try a trial or see plans & pricing

Drugs may be covered by multiple patents or regulatory protections. All trademarks and applicant names are the property of their respective owners or licensors. Although great care is taken in the proper and correct provision of this service, thinkBiotech LLC does not accept any responsibility for possible consequences of errors or omissions in the provided data. The data presented herein is for information purposes only. There is no warranty that the data contained herein is error free. thinkBiotech performs no independent verification of facts as provided by public sources nor are attempts made to provide legal or investing advice. Any reliance on data provided herein is done solely at the discretion of the user. Users of this service are advised to seek professional advice and independent confirmation before considering acting on any of the provided information. thinkBiotech LLC reserves the right to amend, extend or withdraw any part or all of the offered service without notice.