THERAPEUTIC SUBSTANCES Background of the Invention A. Field of the Invention The invention relates to therapeutic agents for internal administration to an animal body such as a human and to methods of their manufacture and administration.

B. Prior Art Internally administered therapeutic agents usually ^' encompass drugs and other non-living materials which are ingested by a user, or implanted or inserted in the user for therapeutic purposes. They are delivered to the body of the user in a variety of ways, such as in the form of capsules for oral administration or or by insertion as suppositories, or in the form of liquids for oral administration or injection, among other techniques. Also, living organisms have been administered by injection e.g., small pox, vaccination, or- by the oral route in the form of liquid droplets e.g., Sabin polio immunization. These agents are prepared by a variety of manufacturing processes, and are stored until their administration to the end user. Presently, through techniques of genetic engineering, living organisms can be genetically programmed to produce therapeutic substances such as interferon, antibiotics, and insulin. These programmed organisms are subjected to a complex fermentation, extraction, and purification process

before the therapeutic substance is administered to the patient. Moreover, since there is uncertainty about the potential pathogenicity of genetically altered organisms (viruses, bacteria, or yeast for example) , elaborate safeguards have been enforced to prevent these altered organisms from contacting or "infecting" people. However, by deliberately selecting non-pathogenic organisms for genetic manipulation, or other organisms with finite longevity, the safety precautions have been able to be relaxed as contamination fears have lessened. ^* Description of the Invention

A. Objects of the Invention Accordingly, it is an object of the invention to provide an improved mechanism for administering selected therapeutic agents derived from genetically altered organism to an animal body. Further, it is an object of my invention to provide an improved method of generating therapeutic agents derived from genetically altered organisms for administration to an animal body.

B. Detailed Description of the Invention In accordance with the invention genetically programmed organisms which produce the desired therapeutic agents to be administered to an animal m body such as a human are prepared in situ and enclosed within a protective membrane providing mechanical confinement to the organisms while they are being administered to the animal body. The membrane may include an inner layer containing material providing sustenance to the enclosed bacteria for at least the

time they are outside the human body, or a nutrient material may be included in the organism section of the chamber itself. Alternatively, a microporous membrane that contains the organisms but allows passage of nutrients from a nutrient source or culture medium may be employed. The membrane and its contents (hereinafter referred to collectively as a "capsule") may be orally ingested by the human, or may be inserted as a suppository or otherwise implanted within the body. The capsule may either remain intact, exchanging its therapeutic product for nutrients until removed or excreted, or may dissolve, allowing the therapeutic organisms to colonize the target areas releasing their therapeutic products there. In the case of bacteria, a genetically altered strain is preselected that itself produces the therapeutic agent which is to be utilized by the body. For example, altered bacteria of the type E. Coli produce insulin which is used to treat diseases such as diabetes. In one embodiment of my invention, the membrane dissolves within the body to a sufficient extent to release the enclosed bacteria. The bacteria then operate, within the body environment, to produce the selected therapeutic agent [e_.g, insulin]. The number of bacteria are, of course, proportioned to the desired dosage of agent to be administered to the body, taking into consideration the type of bacteria, the specific portion of the body in which they were lodged, and their expected lifetime and productivity time within that body portion. In an alternative embodiment, the therapeutic agent is generated by the bacteria within the membrane and is transferred across the membrane walls by

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1 diffusion, the bacteria remaining within the membrane.

2 in this embodiment, the effective pore size of the

3 membrane is such that the bacteria are prevented from

4 transfer across the membrane wall, while the

5 therapeutic agent which they produce passes relatively

6 freely across this membrane and into the body in

7 exchange for nutrients.

8 In a further embodiment of the invention, a

9 double-walled membrane is used, the bacteria being 0 enclosed within a first or inner wall, and a layer of 1 material providing nourishing sustenance to the 2 bacteria being enclosed between the first. all and a 3 second or outer wall. In this embodiment, as with the 4 previously-described embodiments, the membrane walls 5 may be such as to be dissolvable when ingested or 6 inserted into the body, or may be such that the walls 7 are relatively resistant to degradation within the 8 body but allow passage of therapeutic products 9 generated by the bacteria into the body. Moreover, in 0 the case of dissolvable capsules, they may be modified 1 to dissolve under optimal conditions for specific 2 locality colonization and as such may be acid 3 resistant and more soluable in an alkaline environment 4 for intestinal colonization, or by other physical or 5 chemical modifications designed to enhance successful

26 colonization in their desired area. Furthermore, the

27 capsules may be stored at cold or freezing

28 temperatures to retard bacterial growth until 25. administration.

30 The foregoing and other and further objects and

31 features of this invention will be more readily

32 understood on reference to the accompanying drawings

33 showing an insertable capsule in accordance with the

34 present invention in which:

1 Detailed Description of the Invention

2 Fig. 1 is a cross-sectional view of a

3 therapeutic device having a single membrane wall

4 enclosing selective therapeutic organisms on the

5 interior thereof; and

6 Fig. 2 is a cross-sectional view of a

7 therapeutic device in accordance with the invention

8 having dual a membraneous wall enclosing the -9 organisms. 0 In Fig. 1, a therapeutic device in the form of 1 a capsule comprises a membraneous wall 10 enclosing, 2 on the interior thereof, selected organisms 12 for 3 manufacture of therapeutic agents to be internally 4 administered to a human body. Wall 10 may comprise a 5 material such as gelatin which is essentially 6 impermeable both to the organism and to the 7 therapeutic agents formed thereby, but which is broken 8 down by the body on ingestion or insertion of the 9 device into it or, alternatively, may comprise a 0 material such as a icroporous membrane which has a 1 pore size sufficient to allow passage of the 2 therapeutic agents formed by the organisms through the 3 membrane wall and into the body on ingestion or 4 insertion therein, while blocking escape of the 5 organism therethrough, and which is relatively inert 6 to degradation by the body when ingested or inserted. 7 In the first case, the therapeutic agent is formed 8 within the body largely outside the membraneous wall, - while in the second case the therapeutic agent is formed within the membraneous enclosure. Turning now to Fig. 2, a further alternative version of my invention is shown. A first or inner membraneous wall 20 encloses organisms 22 therein. A second or outer membraneous wall 24 encloses a layer

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of nutrient 26 which provides sustenance to the organism. Alternatively, the inner and outer chamber may be reversed. This embodiment of the invention is expected to be useful in cases where extended pe.riods of time are expected to elapse between the preparation of the device and its ultimate utilization. As was the case with the embodiments of Fig. 1, the membraneous walls 20 and 24 may be selected to allow escape of the enclosed organism 22 into the body following ingestion or insertion, or may be resistant to degradation by the body but sufficiently permeable to the organism that the therapeutic agent generated by the organism escape through these walls, and through the nutrient layer 26. In the latter case, the layer 26 may also, in addition to, or instead of, providing nutrient to the organism 22, provide an absorptive layer which selectively absorbs constituents generated by the organism which it is desired to preclude from passage into the body.

Conclusion From the foregoing it will seen that I have provided an improved therapeutic device incorporating live genetically programmed organisms producing therapeutic agents to a body such as a human body. In some cases, a single dosage will be sufficient to produce a desired agent for extended periods of time. Alternatively, the removal of an intact capsule or the administration of the appropriate antibiotic in the case of the colonized alternative will discontinue the administration of the therapeutic agent. Moreover, complex and costly manufacturing steps including fermentation, extraction, and purification may be avoided altogether. This device also avoids

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many of the problems associated with degradation of therapeutic agent during shipment or storage. It accomodates itself to generation and administration of a variety of therapeutic agents, and is expected to be simple, yet effective in use. Having illustrated and described my invention, I claim: