1. A method for providing numeric outcomes to a game operator, comprising:
receiving a draw request that includes commit data that defines conditions under which random numeric outcomes to be generated will result in a win for a player of a game;
generating, with an electronic processor, a random numeric outcome based on the draw request;
communicating the random numeric outcome to a game operator to be used by the game operator to determine whether a win has occurred in the game;
generating a draw file that includes the random numeric outcome and the commit data;
digitally signing the draw file with a digital signature using a private key;
storing the draw file in an audit log in an electronic memory;
after storing the draw file, retrieving the draw file from the audit log;
verifying that the draw file has not been changed since being stored, wherein verifying that the draw file has not been changed since being stored comprises:
retrieving a public key associated with the private key used to sign the draw file, wherein the public key indicates that the digital signature for the draw file was generated using the associated private key; and
verifying, based on the public key, that the draw file has not been changed since being signed using the private key; and
confirming, based on information in the draw file, that the random numeric outcome resulted in a game win.
2. The method of claim 1, wherein digitally signing the draw file comprises digitally signing the draw file with a private key associated with a current time, and wherein retrieving the public key comprises:
determining a time associated with the draw file; and
retrieving a public key associated with the determined time.
3. The method of claim 1, wherein storing the draw file in an audit log comprises storing the draw file in an audit log that includes a plurality of draw files indexed by time.
4. The method of claim 1, wherein receiving a draw request further comprises receiving a draw request that includes game parameters, wherein the game parameters describe parameters for one or more random numeric outcomes to be generated.
5. The method of claim 1, wherein retrieving the draw file comprises:
receiving an indication that a random numeric outcome included in the draw file resulted in a game win; and
in response to receiving the indication, retrieving the draw file from the audit log.
6. A system for providing numeric outcomes to a game operator, comprising:
an interface module operable to receive a draw request that includes commit data defining conditions under which random numeric outcomes to be generated will result in a win for a player of a game from a remote element and transmit one or more random numeric outcomes to the remote element;
a random number generator operable to:
generate the one or more random numeric outcomes based on the draw request; and
generate a draw file that includes the random numeric outcome and the commit data;
a digital signature generator operable to:
generate a digital signature for the draw file using a private key;
store the signed draw file in an audit log memory;
after storing the draw file, retrieve the draw file from the audit log memory; and
verify that the draw file has not been changed since being stored;
a key memory operable to store a public key associated with the private key, wherein the public key indicates that the digital signature generator generated the digital signature for the draw file using the associated private key; and
the audit log memory operable to store an audit log comprising a plurality of signed draw files, wherein each of the signed draw files includes sufficient information to allow an operator of the system to confirm that the one or more random numeric outcomes included in that draw file resulted in a game win.
7. The system of claim 6, wherein:
the digital signature generator is operable to generate a digital signature for the draw file using a private key associated with a current time; and
the key memory is operable to store a plurality of public keys and a plurality of private keys, wherein the public keys are indexed by time and each public key is associated with one of the private keys.
8. The system of claim 6, wherein the audit log comprises a plurality of draw files indexed by time.
9. The system of claim 6, wherein the interface module is operable to receive a draw request by receiving a draw request that includes game parameters and commit data, wherein the game parameters describe parameters for one or more random numeric outcomes to be generated.
The claims below are in addition to those above.
All refrences to claim(s) which appear below refer to the numbering after this setence.
1. A method of promoting binding of an active agent to a preformed crystalline diketopiperazine microparticle in suspension comprising the steps in the sequence set forth of:
i) modifying the chemical potential of the active agent wherein said modifying allows for an energetically favorable interaction between the active agent and the preformed crystalline diketopiperazine microparticle independent of removal of solvent; followed by
ii) allowing adsorption of the active agent onto the surface of the preformed crystalline diketopiperazine microparticle;
wherein said modifying step causes said adsorbing of said active agent onto a surface of said preformed crystalline diketopiperazine microparticle to provide a coating of said active agent on said preformed crystalline diketopiperazine microparticle; and
wherein said preformed crystalline diketopiperazine microparticle does not comprise an active agent.
2. The method of claim 1 wherein modifying the chemical potential comprises modifying the structure, flexibility, rigidity, solubility or stability of the active agent.
3. The method of claim 2 wherein modifying the chemical potential of the active agent comprises altering solution conditions.
4. The method of claim 3 wherein said active agent is a peptide or a protein and said altering solution conditions comprise adding an active agent modifier to the solution and wherein said active agent modifier is selected from the group consisting of sodium chloride, hexylene-glycol (Hex-Gly), trehalose, glycine, polyethylene glycol, trimethylamine N-oxide, mannitol, proline, methanol, ethanol, trifluoroethanol, hexafluoroisopropanol, NaSCN, (CH3)3N\u2014HCl, Na2NO3, NaClO4, cesium chloride, sodium citrate, and sodium sulfate.
5. The method of claim 4 wherein said active agent modifier is sodium chloride.
6. The method of claim 1 wherein said modifying step comprises dissolving the active agent in a fluid phase of the suspension of preformed crystalline diketopiperazine microparticles and changing the pH of the fluid phase.
7. The method of claim 6 wherein the pH is changed prior to the addition of active agent.
8. The method of claim 6 wherein the pH is changed subsequent to the addition of active agent.
9. The method of claim 4 wherein the active agent modifier improves the structural stability or pharmacodynamics of the active agent.
10. The method of claim 1 wherein the active agent is a protein, peptide or polypeptide.
11. The method of claim 10 wherein the active agent is selected from the group consisting of insulin, ghrelin, growth hormone, and parathyroid hormone (PTH).
12. The method of claim 2 wherein modifying the chemical potential of the active agent comprises modulating one or more energetically favorable interactions with the crystalline diketopiperazine microparticle surface.
13. The method of claim 12 wherein the one or more energetically favorable interactions between the active agent and the crystalline diketopiperazine microparticle comprises an electrostatic interaction.
14. The method of claim 12 wherein the one or more energetically favorable interactions between the active agent and microparticle comprises a hydrophobic interaction.
15. The method of claim 12 wherein the one or more energetically favorable interactions between the active agent and microparticle comprises a hydrogen bonding interaction.
16. The method of claim 1 wherein the diketopiperazine is fumaryl diketopiperazine.
17. The method of claim 1 further comprising a step for removing the solvent after the allowing step.
18. A process for preparing a drug delivery composition comprising an active agent and a crystalline diketopiperazine microparticle comprising the steps in the sequence set forth of:
i) providing an active agent solution comprising an active agent molecule and providing a preformed crystalline diketopiperazine microparticle in a suspension or powder; next
ii) combining said active agent solution with said preformed crystalline diketopiperazine microparticle suspension or powder to form a fluid phase; and
iii) then modifying the chemical potential of the active agent in the fluid phase;
wherein said modifying step causes adsorption of said active agent onto a surface of said preformed crystalline diketopiperazine microparticle to provide a coating of said active agent on said preformed crystalline diketopiperazine microparticle.
19. The process of claim 18 wherein the modifying step allows for interaction between the active agent and the preformed crystalline diketopiperazine microparticle.
20. The process of claim 18 wherein the modifying step comprises adding an active agent modifier to the fluid phase, said active agent comprises a peptide or a protein, and wherein said active agent modifier is selected from the group consisting of sodium chloride, hexylene-glycol (Hex-Gly), trehalose, glycine, polyethylene glycol, trimethylamine N-oxide, mannitol, proline, methanol, ethanol, trifluoroethanol, hexafluoroisopropanol, NaSCN, (CH3)3N\u2014HCl, Na2NO3, NaClO4, cesium chloride, sodium citrate, and sodium sulfate.
21. The process of claim 18 wherein the modifying step comprises the addition of water and wherein said modification decreases the solubility of the active agent.
22. The process of claim 18 wherein the modifying step comprises adding an active agent modifier to the fluid phase and the active agent modifier promotes association between the active agent and a preformed crystalline diketopiperazine microparticle, wherein said active agent modifier is selected from the group consisting of sodium chloride, NaSCN, (CH3)3N\u2014HCl, Na2NO3, NaClO4, cesium chloride, sodium citrate, sodium sulfate, methanol, ethanol, trifluoroethanol, hexafluoroisopropanol, hexylene-glycol, trehalose, glycine, polyethylene glycol, trimethylamine N-oxide, mannitol and proline.
23. The process of claim 18 wherein the modifying step comprises adding an active agent modifier to the fluid phase and the active agent modifier improves the structural stability of the active agent molecule, wherein said active agent modifier is selected from the group consisting of sodium chloride NaSCN, (CH3)3N\u2014HCl, Na2NO3, NaClO4, cesium chloride, sodium citrate, sodium sulfate, methanol, ethanol, trifluoroethanol, hexafluoroisopropanol, hexylene-glycol, trehalose, glycine, polyethylene glycol, trimethylamine N-oxide, mannitol and proline.
24. The process of claim 18 wherein the diketopiperazine is fumaryl diketopiperazine.
25. A process for preparing a drug delivery composition comprising an active agent and a crystalline diketopiperazine microparticle comprising the steps in the sequence set forth of:
i) providing an active agent solution comprising an active agent molecule and providing a preformed crystalline diketopiperazine microparticle in a suspension or powder; next
ii) modifying the chemical potential of the active agent in the active agent solution; and
iii) then combining said active agent solution with said preformed crystalline diketopiperazine microparticle suspension or powder to form a fluid phase wherein said modifying step causes adsorption of said active agent onto a surface of said preformed crystalline microparticle to provide a coating of said active agent on said preformed crystalline diketopiperazine microparticle.