WO2001043698A1

WO2001043698A1 - Topical ointment

Info

Publication number: WO2001043698A1
Application number: PCT/US2000/034185
Authority: WO
Inventors: Donald R. Carter; Stephen M. Mitchell
Original assignee: Carter Donald R; Mitchell Steven M
Priority date: 1999-12-15
Filing date: 2000-12-15
Publication date: 2001-06-21
Also published as: WO2001043698A9; AU2270801A

Abstract

Topical ointment comprises a base material which itself may comprise mineral oil and polyethylene glycol. Encapsultated within the base material is an aqueous solution. The ointment may further include additional substances encapsulated therein. Application of the topical ointment to a bodily orfice provides for the moisturizing and the slow delivery of the additional substance to the applied area. The ointment interacts with the body hear emitted from the bodily area and dissolves and provides a slow rate of delivery of the materials encapsulated therein.

Description

TOPICAL OINTMENT The present application is a cαntinuation-in-part of

U.S. patent application #09/316,426 filed on May 21, 1999.

FIELD OF THE INVENTION

The present invention relates to a topical ointment ^_and more--particularl-y-^Jto -a—topical- ointment- which may act as a moisturizer and delivery system of substances to bodily areas upon which it is applied.

BACKGROUND OF THE INVENTION

There currently exists a number of different methods and apparatus for delivering drugs and other pharmaceuticals to parts of the human body. In oral delivery of the drug, the active agent enters the bloodstream by being absorbed in the lining of the stomach. Another drug delivery system is through direct injection via a needle into the bloodstream. Other possible, drug delivery systems include (a) administration of a suppository, endotracheal administration, and eye dropping administration. Disadvantages of the above described methods may include lack of absorption of the drug through stomach lining, the pain experienced from injections, and the inability to deliver measured amounts of the drugs over predetermined periods of time. Another method of delivering a drug or pharmaceutical is through application of a substance carrying the drugs or pharmaceuticals to a ucosal surface of the body. The drug or other pharmaceutical composition may be mixed with a petroleum-based jelly and the combination topically applied to a mucosal surface, such as those in the nasal passageway. As is documented, the placement of petroleum- based products in the airways, may have certain medical side effects.

SUMMARY-OF- THE NVENTION The inventors have recognized that a topical ointment may be provided which upon application to various bodily surfaces may provide moisturization. In situations where the ointment includes additional substances such medications, the ointment may further provide for the controlled delivery of these substances to surfaces upon which the ointment has been applied. The inventors have further recognized that upon application of the topical ointment to different bodily cavities, the delivery of the additional substances to the surfaces within the cavity may be performed at a slow release rate.

The topical ointment described herein may include a base material which may be comprised of a combination of mineral oil and polyethylene glycol. Encapsulated within the base material may be a predetermined quantity of an aqueous solution such as bacteriostatic water. Other aqueous solutions which may be encapsulated include a mixture of NaCl with sterile H,0. Also encapsulated within the base material may be an additional substance which may include, but is not limited to various drugs or pharmaceutical substance such as antibiotics, steroids, aromatic oils, nitroglycerine, painkillers, nicotine and hu alog insulin.

In the manufacture process for the topical ointment, a predetermined quantity of the base material is placed in

-a- -device -which acts -to -mix, bea-t, whip-,- blend and/or s-t-ir the materials contained therein. The material is mixed at a predetermined rate to control the size of the encapsulations formed therein. The lower the rate at which - the mixing process may occur the smaller the encapsulations created in the base material. The percentages of the aqueous solution versus the additional materials encapsulated may be varied to control the concentration of the additional substances to be delivered. Further, the percentage of the base material versus the other elements may also be changed to vary the delivery rate.

Cnce the mixing process is begun, predetermined portions of the aqueous solution may be added. The mixing process may act to encapsulate the aqueous solution within the encapsulations created in the base material. Additional portions of the aqueous solution may be added to the base material during the mixing process until each portion is encapsulated within the base material.

Upon encapsulation of the desired amount of aqueous solution within the base material the ointment may be employed as a moisturizer. Alternatively, additional substances may also be encapsulated during a further mixing process. Predetermined portions of the additional substance may be added to the base material and aqueous solution during the mixing process. All portions of the additional substance may be added until the entire amount is encapsulated.

-In use, t-op-ical ointment- -may-—be- applied -to-— a-r-ious-- bodily surfaces. When the ointment comes in contact with the bodily surface, body heat may act to dissolve the base material providing for the release to the surface of the - aqueous solution and other substances encapsulated therein. The rate the base material dissolves may be related to the proximity of that portion of the ointment to the bodily surface as well as other environmental factors.

As the base material dissolves the materials encapsulated within the base material are delivered to the bodily surface. This continuous exposure act to hydrate the affected area as well as provide exposure to the additional substances. Through this exposure medications may be absorbed into the blood stream.

DETAILED DESCRIPTION Disclosed herein is a topical ointment which may be applied to various parts of the human body, and through exposure to body heat, provide delivery of moisturizing agents as well as other substances. In general, the topical ointment comprises a base material which is combined with an aqueous solution which may provide hydration upon application. Also included may be additional substances such as a medications or aromatic oils which when encapsulated within the topical ointment provides for a slow release of the substance to a bodily surface.

The topical ointment includes a base material which may. be ..comprised of..mineral .oil and....pαlyalkylene ..(.e.g., polyethylene giycol) . This material may be known as plasticized base, which is manufactured by Professional Compounding Associates of Houston Texas. Plasticized base may comprise approximately five percent of a low-molecular weight polyethylene giycol and approximately ninety-five percent mineral oil. The polymer is soluble in mineral oil above ninety degrees Fahrenheit, which is close to its melting point. When the solution is cooled below ninety degrees Fahrenheit the polymer precipitates and causes gelatin.

A first element encapsulated in the topical ointment may be an aqueous solution. The aqueous solution may also comprise approximately 0.9% NaCl, and the remaining portion sterile H₂0. This aqueous solution may include other compounds which the ointment may deliver upon application to a bodily surf ce . With regards to additional substances which may be encapsulated in the base material, these may include a large variety of drugs, oils, dietary supplements and other medications. The desired substances may be selected from a group of nontoxic, water soluble or miscible materials that are capable of being absorbed through the human skin. One type of substance which may be encapsulated in the topical ointment are antibiotics. The antibiotic may include: Gentamycin, Tetracycline, Ξrythromycin, Cephalexin.

Anotier substance .which may_b.e ..encapsulated...in. the ointment includes steroids. The group steroids may include: Prednisone, Dexa ethasone, Prednisolone.

Yet another substance which may be encapsulated in the base material includes aromatic oils. These oils may be employed in treatments such as aroma therapy. The oils may include: Eucalyptus Oil, Rosemary Oil, Pine Needle O l, Tea Tree Oil, Wintergreen Oil, Peppermint Oil, Spearmint Oil, Camphor Oil, Sage Oil, Jojoba Oil, Cinnamon Oil, Anise Oil, Lemon Oil, Lime Oil, Orange Oil, Clove Oil, Almond Oil, White Pine Oil, Cardamon Oil and Cedar Leaf oil.

Still yet another substance which may be encapsulated within the base material are dietary supplements. These supplements may include: various vitamins, iron, potassium, calcium, potassium, magnesium, copper, zinc.

Other substances which may be encapsulated include various medications. These medications may include: humalog insulin, anti-nausea medication (Prochloroperazine or Promethazine) , smoking prevention medication (nicotine resin) , painkilling medication (codeine, hyrocodone) , nitro-glycerin .

In use, the formulation for the topical ointment may comprise approximately 50-80! by weight of the base material. Additionally, the formulation may comprise approximately 0-50% by weight of the aqueous solution. In formulations where an additional substance is included, 0- 3QSLJay ..weight of..the -additional substance may be included. With regards to the various substances described above, the composition of the topical ointment is such that one or more different substances (for example antibiotics and aromatic oils) may be encapsulated therein. As described above, the ointment may be used without encapsulating any additional substances. Provided below are the steps which describe the creation of the ointment. The ointment may be prepared by continuous or batch processes. As in preparing conventional emulsions, shear force may be applied to the components by use of mixers, blenders, homogenizers, mills, impingement surfaces, ultra-sound, shaking or vibration. To get the desired encapsulations within the base material, the mixing shear should be at low levels. The higher the shear the larger the encapsulations. Temperature is not usually a critical factor in the preparation of the systems. In particular, the steps to manufacture the ointment include the encapsulation of the aqueous solution and any additional substances within the base material. As an example, a quantity of the base material (Plasticized Base) is placed in a mixing device such as commercially know table top mixer, like the type manufactured by 'companies such as Sunbeam. A whipping or mixing process is then performed on the base material at a low sheer rate. The rate at which the base material is mixed or wjhipped is directly related to the size of the encapsulations created within the material. As- mentioned above, - the- -faster and shorter the mixing process, the larger the encapsulations will be. The size of the encapsulations is relevant because this is directly related to the rate at iwhich the aqueous solution and the additional substa'nces are delivered to the bodily area to which the ointment is applied. Initially the base material is mixed in the container until encapsulations of the desired size are fornjied. This determination may made through a visual or other examination of the base material. During the mixing process, a predetermined quantity of the aqueous solution is added during the mixing process to hydrate the base material. The entire amount of the aqueous solution may be added at once, or it may be added in separate portions to avoid any loss of solution due to splashing or other effects . Upon the addition of the aqueous solution, the base material mixture is monitored to detect when the desired amount aqueous solution has been encapsulated therein. One sign tnat encapsulation is complete, is the lack of standing liquids in the container employed for mixing.

If additional substances are to be added, the mixing of the base materials continues after encapsulation of the aqueous solution. A quantity of the additional substances is then added. If loss of the additional substance may be a problem (i.e., due to splashing, etc.) the additional substa_n.ce._may be . added, .in predetermined . portions.. . t should be noted that the above process may be performed at room temperature however, the ambient temperature should not to exceed the melting temperature of the base material.

The percentages of the base material, aqueous solution, and additional substances used during the formulation process can be varied depending upon the type of additional material employed and the desired rate of delivery of the encapsulated materials. For example, if the percentage of base material versus aqueous solution and additional substances is increased, the delivery rate will be increased. Conversely, if the percentage is decreased, the rate of delivery will increase.

In use, the ointment can be applied directly to various bodily surfaces. As was described above, the base material has a melting temperature of approximately ninety degrees Fahrenheit. Upon application to a bodily surface, the body heat, which may be approximately ninety-five to one hundred degrees Fahrenheit will begin to dissolve the bonds of the polyethylene giycol in the Plasticized base, which in turn releases an amount of the encapsulated aqueous solution and additional substance, if encapsulated, to the bodily area. The combination of the aqueous solution and mineral oil act as a moisturizing element for the exposed area.

The slow release of the aqueous solution and additional substances is made possible by the fact that due to the -chemical ma-ke-up-o-f the -polyethylene -giycol, -it will retain its structure and bond the mineral oil and hold the encapsulated material until a melting temperature is reached. When an amount of the ointment is applied to a • bodily area, the portion of the ointment in contact with the skin will have a higher temperature than the amount which is further from the skin. In practice the portion of the ointment next to the skin will dissolve delivering ts encapsulated material to the area while the portions away from the skin will remain cooler and thus retaining the encapsulated materials.

For example, the ointment has special applicability for use within the nasal cavity upon the nasal mucosa. Upon application, the portion in contact with the skin will dissolve and deliver the encapsulated materials. Conversely, the portion o£ the ointment exposed to the air will stay in the gelatinous state due to, m most cases, the lower ambient temperature of the air. The cooler temperatures are also due to evaporative cooling effects which are caused by the movement of air through the nasal cavity. This provides the benefit that the entire amount of ointment applied to the bodily surface does not dissolve and expose the entire amount of the encapsulated material to the area at once. All of the dissolved materials may be absorbed by the skin and the delivery of the additional substance to the bloodstream may occur. The ointment may be applied to other mucosal surfaces (vagina, rectum) but the. rate of..delivery .may • be- greater due., to-- he--lack of moving air. EXAMPLE 1

Plasticized base 500g (66.67% by weight) Bacteriostatic H₂0 193.75g (25.93% by weight) Gentamycin 56. 5g (7.5% by weight) In the manufacture of one formulation of the topical ointment, 500 grams of Plasticized base may be placed in the mixing apparatus, such as a table top mixer. The mixer is started at a low sheer rate and the Plasticized base is mixed until the desired encapsulations are formed. With 500g of the material, it may take approximately 1 hour. The next step is to add all or a portion of the 193.75 cc's of bacteriostatic H₂0 to the Plasticized base. The mixing process is monitored to note when the desired amount of the bacteriostatic H₂0 is encapsulated within the Plasticized base. With the above recited amounts, the encapsulation of the bateriostatic water may take approximately 8 - 12 hours .

- - When the encapsulation process of the bacteriostatic water is complete, the mixing process is continued, and the antibiotic, Gentamycin, is added. In this formulation, three milligrams per gram of Gentamycin are included. This equates to 56.25 grams of the antibiotic, which when fully encapsulated after the mixing process generates seven hundred and fifty grams of the topical ointment. -Encapsulation- -of--the- Gentamycin- may -take approximately -3- 4 hours . Upon completion of the mixing process, the ointment is ready for topical use. If the ointment is to be applied in the nasal cavity, a typical dosage may be 0.5g per nostril. Upon application, the total amount may dissolve in approximately 8-12 hour period. The dosage of the antibiotic in the ointment is approximately the same amount of the drug as if it had been prescribed orally. In situations where a higher dosage of an additional substance is called for, the amount of aqueous solution may be varied to compensate. The foregoing description of the present invention has been presented for purposes of illustration and description. Furthermore, the description is not intended to limit the invention to the form disclosed herein. Consequently, variations and modifications commensurate with the above teachings, and the skill or knowledge of the relevant are, within the scope of the present invention. The embodiments described hereinabove are further intended to explain best modes known for practicing the invention and to enable others skilled in the art to utilize the invention in such, or other, embodiments and with various modifications required by the particular applications or uses of the present invention. It is intended that the appended claims be construed to include alternative embodiments to the extent permitted by the prior art.

Claims

1. A topical ointment for application to a bodily comprising a base material, where an amount of an aqueous solution is encapsulated in the base material. 2. The topical ointment of claim 1 further including at least one additional substance encapsulated in the base material.

-3.- The topical ointment of claim -2- comprising .-- approximately 50-80% by weight of the base material; approximately 0-30% by weight of the aqueous solution; approximately 0-10% by weight of the additional - substance.

4. The topical ointment of claim 1 wherein the aqueous solution is bacteriostatic water. 5. The topical ointment of claim 1 wherein the aqueous solution is approximately 0.9% NaCl, and a remaining portion sterile H₂0.

6. The topical omtment of claim 2 wherein the additional substance includes at least one of: an antibiotic, steroid, humalog insulin, nitro-glycerin, aromatic oils, anti-nausea medication, pain killers, dietary supplements, smoking cessation medication.

7. The topical ointment of claim 2 wherein the localized area of the body to which the ointment is applied is the nasal cavity. θ. The topical ointment of claim 6 wherein body heat emitted by the localized body area dissolves the base material to provide a slow delivery of the additional substance.

9. The topical ointment of claim 5 wherein the antibiotic may be selected from a group comprising: Gentamycin, Tetracycline, Erythromycin, Cephalexin.

10. The topical ointment of claim 5 wherein the steroids may be selected from a group comprising: Prednisone, Dexa e-thasone, Prednisolone .

11. The topical ointment of claim 5 wherein the aromatic oils are selected from the group comprising

Eucalyptus Oil, Rosemary Oil, Pine Needle Oil, Tea Tree Oil, Wintergreen Oil, Peppermint Oil, Spearmint Oil, Camphor Oil, Sage Oil, Jojoba Oil, Cinnamon O l, Anise Oil, Lemon Oil, Lime Oil, Orange Oil, Clove Oil, Almond Oil, White Pine Oil, Cardamon Oil and Cedar Leaf oil.

12. The topical ointment of claim 5 wherein the dietary supplements are selected from the group comprising: vitamins, iron, potassium, calcium, potassium, magnesium, copper, zinc. 13. The topical ointment of claim 1 wherein the base material is Plasticized base.

14. The topical ointment of claim 1 wherein the base material approximately 95% mineral oil and 5% polyethylene giycol.

15. A method of preparing a topical ointment comprising the steps of: mixing a first quantity of a base material in a container for until a desired size of encapsulation is formed in the base material, and adding a second quantity of an aqueous solution to the container and continuing the mixing of the base material and the aqueous solution until a first desired amount of the aqueous solution is contained within the encapsulations of the base material.

16. The method of claim 15 further comprising the step of adding at least one additional substance to the container and continuing the whipping of the base material until a second desired amount of the at least one additional substance is contained within the encapsulations, along with the first desired amount of the aqueous solution, within the base material.

17. The method of claim 16 further comprising the step of applying the ointment to a bodily region. 18. The method of claim 17 wherein the bodily region is the nasal cavity.

19. The method of claim 16 wherein the ointment comprises : approximately 50-80% by weight of the base material; approximately 0-50% by weight of the aqueous solution; and approximately 0-30% by weight of the at least one additional substance.

20. The method of claim 16 wherein the aqueous solution is bacteriostatic water. 21. The method of claim 16 wherein the aqueous solution is approximately 0.9% NaCl with a remaining portion sterile H-O.

22.- The-method -of -claim 16 wherein- the at least -one- additional substance includes at least one of: an antibiotic, steroid, humalog insulin, nitro-glycerin, aromatic oils, anti-nausea medication, pain killers, dietary supplements, smoking cessation medication.

23. The method of claim 17 wherein body heat emitted by the body area dissolves the base material which provides for delivery of the aqueous solution and the additional substance to the bodily area.

24. The method of claim 22 wherein the antibiotic may be selected from a group comprising: Gentamycin, Tetracycline, Erythro ycin, Cephalexin. 25. The method of claim 22 wherein the steroids may be selected from a group comprising :Prednisone, Dexamethasone, Prednisolone.

26. The method of claim 22 wherein the aromatic oils may be selected from the group comprising: Eucalyptus Oil, Rosemary Oil, Pine Needle Oil, Tea Tree Oil, Wintergreen Oil, Peppermint Oil, Spearmint Oil, Camphor Oil, Sage Oil, Jojoba Oil, Cinnamon Oil, Anise Oil, Lemon Oil, Lime _Oil, Orange Oil, Clove Oil, Almond Oil, White Pine Oil, Cardamon Oil and Cedar Leaf oil.

27. The method of claim 22 wherein the dietary supplements are selected from the group comprising: vitamins, iron, potassium, calcium, potassium, magnesium, copper, zinc.

28. The method of claim 15 wherein the base material is .Plasticized. base.

29. The method of claim 15 wherein the base material comprises approximately 95% mineral oil and 5% polyethylene giycol .

30. A method of delivery of a substance to a bodily area comprising: providing a ointment comprising a base material, where an amount of an aqueous solution an additional substance is encapsulated in the base material; and applying a predetermined amount of the ointment to the bodily area.

3.1. The.___meth.ad_..of claim 29 wherein the .base material is Plasticized base.