You can patenting a combination of two compounds or you can filing an application for a new substituent (such as a Markush claim) or you can protect a new use of a known compound for the preparation of a new medicament. In some cases you can also protect a carrier or a molecule to facilitate the uptake of a particular compound in the cell. In all these cases you'll have to prove the novelty and the inventive step of your invention, supported by empirical data and specific embodiments. So, the way you describe 'add some drugs in the present formulations' should create a synergetic effect in order to overcome the inventive step or obviousness condition. Concentrations, dosages or regimes can be inventive but are very often associated with the way of applying, such as capsule, perfusion, ointment,... Another application can have some advantages regarding the state-of-the-art, but this should then be illustrated and supported by examples. However, be careful because you can perfectly obtain a patent for a combination of compounds A + B, but you can't commercialize the combination if one or both of the two compounds are still under a valid patent protection for those countries where you'll like to marketing your product in the framework of your freedom-to-operate.
"Small change" is not a defined term. In the United States the change must be "nonobvious." You can go to USPTO.gov and look at the Manual of Patent Examining Procedure (MPEP). Chapter 21 is "Patentability." There you will find a description of the large number of criteria for determining what is or is not obvious. The US Patent Office understands that everything is obvious in the light of hindsight. The US rules remove the use of hindsight in the analysis as much as possible.