Controlled release of pharmacologically active agents from an absorbable biologically compatible putty-like composition

• US 4,650,665 A
• Filed: 10/28/1985
• Issued: 03/17/1987
• Est. Priority Date: 02/08/1985
• Status: Expired due to Term

• Current Assignee: Ethicon Incorporated (Johnson & Johnson)
• Original Assignee: Ethicon Incorporated (Johnson & Johnson)
• Inventors: Levy, Alan, Kronenthal, Richard L., Mattei, Frank V.
• Primary Examiner(s): Rose, Shep K.
• Application Number:
  US06/791,969
• Time in Patent Office: 505 Days
• Field of Search: 424/19-22
• US Class Current: 424/435
• CPC Class Codes: A61K 9/0063 Periodont
• CPC Class Codes: A61K 9/2013 Organic compounds, e.g. phospholipids, fats
• CPC Class Codes: A61K 9/205 Polysaccharides, e.g. alginate, gums; Cyclodextrin

Abstract

An absorbable biologically compatible putty-like composition is used as a matrix from which immunologically or pharmacologically active agents, such as antibiotics, can be introduced into the body to provide a slow sustained release of the agent over an extended period of time. A preferred matrix comprises a mixture of calcium stearate, dextran and castor oil.

Claims

1. In a pharmaceutical depot composition for administration of at least one pharmacologically or immunologically active agent released slowly over an extended period of time at reasonably effective and predictable levels, which comprises a combination of

(a) from 0.25% to 50% by weight of the composition of a pharmacologically or immunologically active agent in an effective depot amount greater than the single dose amount, and

(b) a matrix which is minimally reactive towards body tissue and which is absorbable in the body over an extended period of time without adverse body reaction;

the improvement comprising employing as said matrix an absorbable composition having a putty-like consistency at room and body temperatures, said matrix being completely free of fibrous materials, said matrix comprising between about 35% and 60% by weight of calcium stearate, between about 10% and about 35% by weight of dextran, the remainder of said matrix comprising castor oil.

3. The composition of claim 1 in which the matrix comprises an absorbable bone wax which has a tackiness sufficient for it to adhere readily to a bloody bone surface.

4. The composition of claim 1 in which said pharmacologically or immunologically active agent is selected from the group consisting of anti-microbial agents, anti-cancer agents, antigenic/immunogenic agents, antipsychotic agents, anti-anxiety agents, anti-depressants, stimulants, analgesics, anorexigenic agents, magnetic particles used for hyperthermia treatment, bone growth factors, pharmacodynamic agents, chemotherapeutic agents, agents affecting metabolic diseases, hormones, steroid and non-steroidal anti-inflammatory agents, anti-arthritic agents, vitamins, dietary supplements including metals to combat anemia, anti-epilepsy agents, endocrine agents and fertility control agents.

6. The composition of claim 1, which includes two or more different pharmacologically active agents.

7. The composition of claim 6, which includes an anti-bacterial agent combined with an anti-inflammatory agent and a pain killer.

12. The composition of claim 1 in which said pharmacologically active agent comprises meclocycline sulfosalicylate.

13. In the process of releasing a controlled effective amount of a parenteral depot pharmacologically or immunologically active agent in an animal or human being over an extended period of time, the improvement comprising administering the composition of claim 1 to said animal or human.

2. In a pharmaceutical depot composition for administration of at least one pharmacologically or immunologically active agent released slowly over an extended period of time at reasonably effective and predictable levels, which comprises a combination of

(a) from 0.25% to 50% by weight of the composition of a pharmacologically or immunologically active agent in an effective depot amount greater than the single dose amount, and

(b) a matrix which is minimally reactive towards body tissue and which is absorbable in the body over an extended period of time without adverse body reaction;

said matrix comprising between about 38% and 42% of calcium stearate, between about 28% and 31% of spray dried dextran, and between 27% and 30% of castor oil, said composition having a putty-like consistency at room and body temperatures.

5. The composition of claim 2 in which said pharmacologically active agent comprises from 0.25% to 10% by weight of said composition.

8. In a periodontal disease gum treating method for administration of at least one pharmacologically or immunologically active agent released slowly over an extended period of time at reasonably effective and predictable levels to infected or target area pockets between the base of a tooth and the adjoining periodontal tissues, which comprises a combination of

(a) from 0.25% to 50% by weight of the composition of a pharmacologically or immunologically active agent in an effective depot amount greater than the single dose amount, and

(b) a matrix which is minimally reactive towards body tissue and which is absorbable in the body over an extended period of time without adverse body reaction;

the improvement comprising employing as said matrix, dispensed in the shape of a rod, pellet disc or tiny gum drop, to a pocket formed by teasing the gum away from the tooth, an absorbable composition having a putty-like consistency at room and body temperatures, said matrix being completely free of fibrous materials, said matrix comprising between about 35% and 60% by weight of calcium stearate, between about 10% and about 35% by weight of dextran, the remainder of said matrix comprising caster oil.

9. The method of claim 8 in which said pharmacologically active agent comprises meclocycline sulfosalicylate.

10. The method of claim 8 in which the matrix comprises an absorbable bone wax which has a tackiness sufficient for it to adhere readily to a bloody bone surface.

11. The method of claim 8 in which said pharmacologically active agent comprises from 0.25% to 10% by weight of said composition.