Systems and methods for delivery of materials

• US 8,524,259 B2
• Filed: 12/03/2008
• Issued: 09/03/2013
• Est. Priority Date: 12/05/2006
• Status: Active Grant

• Current Assignee: Landec Corporation
• Original Assignee: Landec Corporation
• Inventors: Taft, David D., Bitler, Steven, Zheng, Qiang, Tzannis, Stelios, Bell, Adam, Dai, Wei-Guo, Ottensmann, Sandra N., Balachander, Natarajan
• Primary Examiner(s): Wax, Robert A
• Assistant Examiner(s): CRAIGO, WILLIAM A
• Application Number:
  US12/746,178
• Publication Number:
  US 20110009571A1
• Time in Patent Office: 1,735 Days
• Field of Search: None
• US Class Current: 424/401
• CPC Class Codes: A61K 9/0019 Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner non-active ingredients are additionally classified in A61K47/00
• CPC Class Codes: A61K 9/0024 Solid, semi-solid or solidifying implants, which are implanted or injected in body tissue compositions for intravenous administration, normal injectable solutions or dispersions for, e.g. subcutaneous administration A61K9/0019; brain implants A61K9/0085; (coated) prostheses, catheters or stents A61L
• CPC Class Codes: A61K 9/146 with organic macromolecular compounds
• CPC Class Codes: A61P 25/18 Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]

Abstract

Systems and methods for delivering release materials, for example drugs and other bioactive materials. Crystalline polymeric systems, referred to as CYC carriers, are associated with the release materials, through chemical bonding or through physical association. The crystallinity of the CYC carriers results from the presence of crystallizable side chains, for example long chain n-alkyl moieties, which results in relatively low and sharp melting temperatures. One class of CYC carriers, referred to as CYSC polymers, have a majority of the crystallizable side chains pendant from the polymer backbone. Another class of CYC carriers referred to as ECC polymers, have a majority of the crystallizable side chains attached to terminal units of the polymer backbone. The ECC polymers can for example be obtained by modification of PLGA polymers. The CYC carriers in another class of non-polymeric. Some CYC carriers, referred to as CYC assemblies, have enhanced crystallinity as a result of the physical association of crystallizable moieties which are present in different types of molecule, for example between a polymer containing crystallizable moieties and a monomer containing crystallizable moieties. For some uses, particularly the delivery of drugs, a bioerodable CYC carrier is preferably used.

Claims

1. A composition which comprises an end cap crystalline (ECC) polymer and a release material associated with the ECC polymer, the release material being (1) one or more bioactive materials which are useful in agricultural applications and which are selected from the group consisting of fertilizers, biocides, insecticides and fungicides or (2) one or more additives which are useful in personal care compositions and which are selected from the group consisting of UV absorbers, fragrances, biocides, antimicrobial agents, germicides, antioxidants, preservatives, disinfectants, enzymes, nutrients and minerals, wherein the ECC polymer

(A) comprises a plurality of polymeric molecules each of which consists essentially of

(i) a polymer backbone which comprises a plurality of repeating units having the formula

—

CF¹F²—

CO—

O—

 

 

(1)

wherein

F¹ is hydrogen and F² is hydrogen or methyl, the repeating units being the same or different, and

(ii) at least one terminal unit which has the formula

-b-Cy 

 

(2)

the Cy moieties in said terminal units providing at least 50% by weight of the Cy moieties in the polymeric molecules, and

Cy being a moiety which is (a) associated with other Cy moieties to provide the ECC polymer with crystallinity and (b) is a moiety which consists of (i) an n-alkyl moiety containing 14-50 carbon atoms, or (ii) a moiety which consists of an n-alkyl moiety containing 14-50 carbon atoms and a polyoxyalkylene moiety, and

b is a bond or a moiety which has a valence of at least 2, which links the Cy moiety to the polymer backbone and which optionally contains additional Cy moieties;

wherein each terminal unit having formula (2) is a moiety selected from the group consisting of

(2A) moieties (i) in which b is a bond, (ii) which have the formula —

Cy and (iii) which are directly linked to the terminal —

CO—

O—

moiety of one of the repeating units having formula (1),

(2B) moieties (i) in which b is a moiety having the formula —

O—

CO—

, (ii) which have the formula

—

O—

CO-Cy

and (iii) which are directly linked to the terminal —

CF¹F²—

moiety of one of the repeating units having formula (1), and

(2C) moieties (i) in which b is a moiety having the formula —

R_pbalc—

O—

CO—

, (ii) which have the formula

—

R_pbalc—

O—

CO-Cy

where R_pbalc is the residue of a polyol of and (iii) which are directly linked to the terminal —

CO—

O—

moiety of one of the repeating units having formula (1); and

(B) has a crystalline melting temperature, Tp, of at least 0°

C. and a heat of fusion, Δ

H, of at least 3 J/g which result from association of the Cy moieties, Tp and Δ

H being measured on a differential scanning calorimeter.

2. A composition according to claim 1 wherein the ECC polymer

(A) has a crystalline melting temperature, Tp, of at least 40°

C., an onset of melting temperature, To, such that the value of (Tp−

To) is less than Tp^0.7, and a heat of fusion of at least 5 J/g, Tp, To and Δ

H being measured on a differential scanning calorimeter (DSC) and

(B) has a number average molecular weight, Mn, of less than 10,000.

3. A composition according to claim 1 wherein at least some of the polymeric molecules contain at least three Cy moieties, and the polymer has a heat of fusion of at least 10 J/g.

4. A composition according to claim 1 wherein at least one of the Cy moieties includes a polyoxyalkylene moiety.

5. A composition according to claim 1

wherein Cy is a moiety which consists of an n-alkyl moiety containing 18-24 carbon atoms, and

wherein the ECC polymer

(i) has a crystalline melting temperature, Tp, of at least 40°

C., an onset of melting temperature, To, such that the value of (Tp−

To) is less than 10°

C., and a heat of fusion of at least 5 J/g, Tp, To and the heat of fusion being measured on a differential scanning calorimeter; and

(ii) has a number average molecular weight, Mn, of less than 8,000.

12. A composition according to claim 1 wherein the release material is selected from the group consisting of fertilizers, insecticides and fungicides.

13. A composition according to claim 12 wherein the release material is one or more of Thiram, fludioxonil, Captan, pentachloronitrobenzene, 2-[(2,6-dimethylphenyl)-(2-methoxy-1-oxoethy)amino] propanoic acid methyl ester, imidacloprid, chlothianidin, dinotefuran and thiomethoxam.

14. A composition according to claim 1 which is selected from the group consisting of deodorants, anti-perspirants, lipsticks, makeups, lotions, creams, oil-in-water emulsions, water-in-oil emulsions, hair care compositions, color care compositions, skin care compositions, sun care compositions, hair styling compositions, hair restyling compositions, shampoos, skin conditioners, nail varnishes, hand creams, night renewal creams, body milks and lotions, light facial creams, protective day creams, liquid moisturizing emulsions, and products designed to remove makeup.

15. A composition according to claim 1 wherein the ECC polymer is mixed with hyaluronic acid.

16. a composition according to claim 1 wherein the release material is an insecticide.

17. A composition according to claim 1 wherein the release material is a fungicide.

18. A composition according to claim 1 which is selected from the group consisting of lipsticks, hair care compositions, hair styling compositions, hair restyling compositions, nail varnishes, and products designed to remove makeup.

19. A method of releasing the release material from a release composition as claimed in claim 1 which comprises subjecting the composition to conditions which change the association between the release material and the ECC polymer.

20. A method of making a release composition as claimed in claim 1 which comprises mixing the release material and the ECC polymer, wherein the release material has a maximum temperature to which it can be exposed without damage, and the release material is mixed with the ECC polymer at a temperature at which the polymer is liquid and which is below the maximum temperature.

21. A method according to claim 20 wherein the mixing is carried out in the absence of any liquid other than the ECC polymer.

6. A composition which comprises an end cap crystalline (ECC) polymer and a release material associated with the ECC polymer, the release material being (1) one or more bioactive materials which are useful in agricultural applications and which are selected from the group consisting of fertilizers, biocides, insecticides and fungicides or (2) one or more additives which are useful in personal care compositions and which are selected from the group consisting of UV absorbers, fragrances, biocides, antimicrobial agents, germicides, antioxidants, preservatives, disinfectants, enzymes, nutrients and minerals, wherein the ECC polymer

(1) comprises a plurality of polymeric molecules each of which consists essentially of

(i) a polymer backbone which comprises a plurality of repeating units having the formula

—

CF¹F²—

CO—

O—

 

 

(1)

wherein

F¹ is hydrogen and F² is hydrogen or methyl, the repeating units being the same or different, and

(ii) at least one terminal unit which has the formula

-b-Cy 

 

(2)

the Cy moieties in said terminal units providing at least 50% by weight of the Cy moieties in the polymeric molecules, and

Cy being a moiety which is associated with other Cy moieties to provide the ECC polymer with crystallinity and being a moiety which consists of (1) an n-alkyl moiety containing 18-24 carbon atoms or (2) an n-alkyl moiety containing 18-24 carbon atoms and a polyoxyalkylene unit, and

b being a bond or a moiety which has a valence of at least 2 and which links the Cy moiety to the polymer backbone, and which optionally contains additional Cy moieties;

wherein each terminal unit having formula (2) is a moiety selected from the group consisting of

(2A) moieties (i) in which b is a bond, (ii) which have the formula -Cy and (iii) which are directly linked to the terminal —

CO—

O—

moiety of one of the repeating units having formula (1),

(2B) moieties (i) in which b is a moiety having the formula —

O—

CO—

, (ii) which have the formula

—

O—

CO-Cy

and (iii) which are directly linked to the terminal —

CF¹ F² —

moiety of one of the repeating units having formula (1), and

(2C) moieties (i) in which b is a moiety having the formula —

R_pbalc—

O—

CO —

, (ii) which have the formula

—

R_pbalc—

O—

CO-Cy

where R_pbalc is i the residue of a polyol, and (iii) which are directly linked to the terminal —

CO—

O—

moiety of one of the repeating units having formula (1), and

(B) has a crystalline melting temperature, Tp, of at least 0°

C. and a heat of fusion, Δ

H, of at least 3 J/g which result from association of the Cy moieties, Tp and Δ

H being measured on a differential scanning calorimeter.

7. A composition according to claim 6 wherein at least one of the terminal units in the ECC polymer has formula 2C and b is a moiety having a formula selected from the group consisting of

—

CH₂—

CH(OH)—

CH₂—

O—

CO—

and —

CH₂—

CH(O—

CO-Cy)—

CH₂—

O—

CO—

.

8. A composition according to claim 6 wherein the ECC polymer is the reaction product of a method which comprises the steps of

(A) reacting

i) a preformed polymer which comprises a plurality of repeating units having the formula (1) and which has a terminal carboxyl group, and

(ii) a polyol, and

(B) reacting the product of step (A) with a carboxylic acid, acid chloride or anhydride containing said Cy moiety.

9. A composition according to claim 6 wherein the ECC polymer is the reaction product of starting materials consisting of

(i) a preformed polymer which comprises a plurality of repeating units having the formula (1) and which has a terminal carboxyl group, and

(ii) an alcohol containing said Cy moiety.

10. A composition according to claim 6 wherein the ECC polymer is the reaction product of

(i) a preformed polymer which comprises a plurality of repeating units having the formula (1) and which has a terminal hydroxyl group, and

(ii) a carboxylic acid, acid chloride or anhydride containing said Cy moiety.

11. A composition according to claim 6 wherein the ECC polymer is the reaction product of a method which comprises the steps of

(A) reacting

(i) a preformed polymer which comprises a plurality of repeating units having the formula (1) and which has a terminal hydroxyl group, and

(ii) a dibasic carboxylic acid or anhydride, and

(B) reacting the product of step (A) with an alcohol containing said Cy moiety.