Drug – bio-affecting and body treating compositions – Preparations characterized by special physical form
Reexamination Certificate
2001-11-09
2004-01-13
Hartley, Michael G. (Department: 1619)
Drug, bio-affecting and body treating compositions
Preparations characterized by special physical form
C424S404000, C428S402000
Reexamination Certificate
active
06676951
ABSTRACT:
FIELD OF THE INVENTION
The present invention relates to processes and formulations capable of protecting, stabilizing, and/or delivering one or more bio-affecting compounds. More particularly, the invention relates to processes of making a composition having a host compound capable of accepting one or more bio-affecting guest compounds and new compositions formed by the processes. The processes are particularly useful in formulating compositions for the topical delivery of the bio-affecting compounds.
BACKGROUND OF THE INVENTION
Biological systems depend on a balance between water-soluble compounds and fat-soluble compounds. Frequently, natural enzymatic reaction will convert a compound to help maintain the balance between water-soluble compounds and lipid-soluble compounds in the biological system, for example, ascorbyl palmitate, which is lipid soluble, can be converted by enzymatic action to ascorbic acid, which is water soluble.
The flow of both water-soluble and lipid-soluble compounds into and out of biological systems are controlled by cell membranes. To penetrate a membrane, a compound needs to have an appropriate structure. In addition, the transfer of the compound across a cell membrane is governed by enzymes, pH, and salt balance. Thus, the cell membranes also help maintain the balance between water-soluble compounds and lipid-soluble compounds in the biological system.
The formation of compositions capable of delivering a compound to a cell membrane and in a structural form or environment that will encourage the transfer of the compound across the cell membrane into the biological system has been the subject of considerable research using many different approaches.
For example, it is known that ascorbic acid (Vitamin C) can be beneficial for healing the skin. In a composition for topical application to the skin, a relatively high concentration of ascorbic acid, preferably at least 8% by weight of the composition, is desirable, and perhaps necessary, to be effective in penetrating the dermal layer and activating collagen in the skin. When the ascorbic acid composition is exposed to air, however, and particularly at such high concentrations, the ascorbic acid tends to rapidly oxidize. A stabilizing environment for the ascorbic acid is necessary to protect it from oxidation or the composition will lose its effectiveness.
It is also known that alpha tocopherol (Vitamin E) can be beneficial for healing and/or preventing damage to the skin by scavenging free radicals in the biological system. In a composition for topical application to the skin, a relatively high concentration of alpha tocopherol, preferably at least 5% by weight of the composition, is desirable, and perhaps necessary, to be effective in penetrating the dermal layer and reducing free radicals. When the alpha tocopherol composition is exposed to air, however, the alpha tocopherol tends to oxidize, that is, become rancid. A stabilizing environment for the alpha tocopherol is necessary to protect it from becoming rancid or the composition will lose its effectiveness.
Considerable research has been conducted on stabilizing ascorbic acid, which is water soluble, and on stabilizing alpha tocopherol, which is lipid soluble. Because of their widely-different solubility characteristics, however, obtaining high concentrations of both in the same composition continues to be a particular challenge. Many compositions for topical application contain low concentrations of both ascorbic acid (as a preservative) and alpha tocopherol (as an antioxidant) at levels below 0.5% by weight. At these low concentrations, however, the ascorbic acid and alpha tocopherol are much less effective in repairing skin damage.
Furthermore, compositions having high concentrations of certain bio-affecting compounds, such as ascorbic acid, have been particularly difficult to stabilize. In this regard, standard stability test procedures that are used to determine the shelf life of a product do not tell the whole story. A standard stability test is conducted at elevated temperatures and humidity is commonly used for determining the shelf life of a composition. Because the rates of chemical reactions and the growth of bacteria tend to double with each 10° C. (18° F.) increase in temperature, testing the stability of a product at elevated temperatures can be used to calculate its expected shelf life at ordinary temperatures with a reasonable degree of confidence. The standard test requires the compound to be placed in the sealed container in which it is to be sold or stored, for 30, 60, and 90 days at 31° C. (87° F.) and at 45° C. (113° F.) in a chamber at 80% relative humidity. This test does not, however, determine the stability of the product after the sealed container has been opened. Unfortunately, many products that pass the shelf-life stability test become unstable in a much shorter period of time once the container has been opened, and quickly lose effectiveness, and worse, may allow the growth of pathogenic bacteria.
Another type of problem encountered in designing topical delivery systems for bio-affecting compounds is encountered when the bio-affecting compound is virtually or totally insoluble in either water or lipids. For example, bio-affecting ingredients for ultra-violet sun block protection include zinc oxide (ZnO) and/or titanium dioxide (TiO
2
), lo which can be used for blocking UV-A and/or UV-B radiation, respectively. Unfortunately, it is difficult to find a carrier for evenly dispersing these insoluble inorganic compounds in a sufficient concentration to form a protective layer over the skin without also imparting a whitening color, which most people find aesthetically undesirable.
There has been a long-felt need for a process of formulating a composition that would be capable of stabilizing at least two different bio-affecting compounds having diverse solubility characteristics. Such a process can be used to stabilize only one bio-affecting compound, but it is expected to have particularly beneficial use when it is desirable to prepare a composition having at least two different bio-affecting compounds of diverse solubility characteristics. There has also been a long-felt need for a process of formulating a composition that is capable of protecting and stabilizing high concentrations of certain bio-affecting compounds that have been particularly difficult to stabilize at such high concentrations. In addition, there has been a particular long-felt need for a process of formulating a composition that is capable of remaining stable for long periods of time, even after the container has been opened causing the composition to be exposed to the ambient air environment. It would also be desirable to produce a composition that discourages the growth of bacteria. These problems have been particularly acute with respect to compositions and products that are expected to be used over an extended period of time after the sealed container has been opened. By way of further example, there has been a long-felt need for a topical delivery system capable of evenly dispersing a bio-affecting compound that is insoluble.
SUMMARY OF THE INVENTION
The formulation processes and compositions according to the invention depend on the initial formation of a host composition having a host capable of accepting a guest in host-guest coordination. One or more bio-active compounds can then be mixed with the host composition for creation of a stable molecular environment, that is, according to a process of molecular stacking. For compositions including water, the formulation processes preferably include establishing a desired pH range to help maintain the stability of pH-sensitive compounds. A wide range of bio-affecting compositions can be made according to the general approach of the invention. In addition, specific formulation processes and compositions are provided.
According to a general aspect of the invention, a process is provided for making a host composition having a host for at least one guest, the process comprising mixing, in any order:
(i) a
Champ Charles Walton
Kinzer Karen June
Crutsinger & Booth
Hartley Michael G.
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