Claims for Patent: 6,107,302
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Summary for Patent: 6,107,302
| Title: | Guanine derivative |
| Abstract: | The invention relates to an anhydrous crystalline form of (2-[2-amino-1,6-dihydro-6-oxo-purin-9-yl)methoxy]ethyl L-valinate hydrochloride (otherwise known as valaciclovir hydrochloride) and a process for preparing it. |
| Inventor(s): | Carter; Barry Howard (Kinston, NC), Partin; Jane Muse (Raleigh, NC), Varlashkin; Peter Gregory (Clayton, NC), Winnike; Richard Augustus (Durham, NC), Grubb, III; William Bayne (Athens, GA), Conway; Gregory Alan (Greenville, SC), Lake; Philip George (Dartford, GB), Skinner; David Michael (Dartford, GB), Whatrup; David James (Dartford, GB) |
| Assignee: | Glaxo Wellcome Inc. (Research Triangle Park, NC) |
| Application Number: | 08/875,173 |
| Patent Claims: |
1. Storage stable Valaciclovir hydrochloride in anhydrous crystalline form and being essentially free of water of hydration including the following d spacing pattern (in
Angstroms): 10.20.+-.0.08, 8.10.+-.0.06, 7.27.+-.0.06, 6.08.+-.0.05, 5.83.+-.0.03, 5.37.+-.0.02, 5.23.+-.0.02, 4.89.+-.0.02, 4.42.+-.0.02, 4.06.+-.0.02, 3.71.+-.0.02, 3.39.+-.0.02, 3.32.+-.0.02, 2.91.+-.0.02, 2.77.+-.0.02.
2. Crystalline valaciclovir hydrochloride as claimed in claim 1 having a water of hydration content of not more than 3% w/w. 3. Crystalline valaciclovir hydrochloride as claimed in claim 2 having a water of hydration content of not more than 2% w/w. 4. Crystalline valaciclovir hydrochloride as claimed in claim 3 having a water of hydration content of riot more than 1% w/w. 5. A method for the treatment of herpes viral infection in a human which comprises administering to the human host, an effective anti-herpes viral amount of storage stable valaciclovir hydrochloride in anhydrous crystalline form and being essentially free of water of hydration as claimed in claim 1. 6. A process for the production of storage stable valaciclovir hydrochloride in anhydrous crystalline form and being essentially free of water of hydration including the d spacings as defined in claim 1, said process comprising treating valaciclovir hydrochloride with an amount of 15% to 40% w/w lower alcohol having 1 to 4 carbon atoms or a lower ketone containing from 3 to 6 carbon atoms serving to convert an amount of said valaciclovir hydrochloride into said anhydrous crystalline form; and then isolating said anhydrous crystalline form. 7. A process for the production of storage stable valaciclovir hydrochloride in an anhydrous crystalline form and being essentially free of water of hydration including the d spacings as defined in claim 1, said process comprising the steps of: a) forming valaciclovir in solution either in free base or salt form; b) converting said free base valaciclovir or salt thereof to valaciclovir hydrochloride; c) isolating valaciclovir hydrochloride from the solution and optionally removing unbound solvent leaving the valaciclovir hydrochloride in substantially dry form; d) treating valaciclovir hydrochloride with 15% to 40% w/w of a lower alcohol having 1 to 4 carbon atoms or a lower ketone containing from 3 to 6 carbon atoms serving to convert an amount of said optionally dried valaciclovir hydrochloride into said anhydrous crystalline form; and e) isolating said anhydrous crystalline form. 8. A process as claimed in claim 7 wherein the lower alcohol is ethanol or a solvent composed substantially of ethanol. 9. A process as claimed in claim 8 wherein the lower alcohol is ethanol or a solvent composed substantially of ethanol and is added in a range of about 17% by weight to about 40% by weight of substantially dry valaciclovir hydrochloride. |
