1. A method for the manufacture of amino polyalkylene phosphonic acid in presence of not more than 0.4% by weight, expressed in relation to the phosphorous acid component (100%), of hydrohalogenic acid, whereby all the available N\u2014H functions in 50% or more of the amine raw material are converted to the corresponding alkylene phosphonic acids, by reacting:
(a): phosphorous acid;
(b): an amine; and
(c): a formaldehyde;
in reactant ratios as follows:
(a):(b) of from 0.05:1 to 2:1;
(c):(b) of from 0.05:1 to 5:1; and
(c):(a) of from 5:1 to 0.25:1;
wherein (a) and (c) stand for the number of moles to be used and (b) represents the number of moles multiplied by the number of N\u2014H functions in the amine, in the presence of an acid catalyst having a pKa equal or inferior to 3.1, said acid catalyst (d) being homogeneous with respect to the reaction medium and being used in reactant ratios as follows:
(b):(d) of from 40:1 to 1:5;
wherein (d) stands for the number of moles of catalyst multiplied by the number of available protons per mole of catalyst, followed by recovering the amino polyalkylene phosphonic acid formed in a manner known per se.
2. The method in accordance with claim 1 wherein the reactant ratios are as follows:
(a):(b) of from 0.1:1 to 1.50:1;
(c):(b) of from 0.2:1 to 2:1; and
(c):(a) of from 3:1 to 0.5:1.
3. The method in accordance with claim 1 wherein the acid catalyst is used in a ratio (b):(d) in the range of from 20:1 to 1:3.
4. The method in accordance with claim 1 wherein the reaction is carried out at a temperature in the range of from 45\xb0 C. to 200\xb0 C.
5. The method in accordance with claim 1 wherein the acid catalyst is selected from the group of sulfuric acid, sulfurous acid, trifluoroacetic acid, trifluoromethane sulfonic acid, methane sulfonic acid, oxalic acid, malonic acid, p-toluene sulfonic acid and naphthalene sulfonic acid, and mixtures thereof.
6. The method in accordance with claim 1 wherein the reactant ratios are as follows:
(a):(b) of from 0.4:1 to 1.0:1.0;
(c):(b) of from 0.4:1 to 1.5:1; and
(c):(a) of from 2:1 to 1.0:1.
7. The method in accordance with claims 1 and 5 wherein the acid catalyst is used in a ratio (b):(d) in the range of from 10:1 to 1:2.
8. The method in accordance with any of the foregoing Claims wherein the reaction is carried out at a temperature in the range of from 70\xb0 C. to 150\xb0 C. combined with an approach selected from:
conducting the reaction under ambient pressure with or without distillation of water and non-reacted formaldehyde;
in a closed vessel under autogeneous pressure built up;
in a combined distillation and pressure arrangement whereby the reaction vessel containing the reactant mixture is kept under ambient pressure at the reaction temperature followed by circulating the reaction mixture through a reactor operated under autogeneous pressure built up thereby gradually adding the formaldehyde and other selected reactants in accordance with needs; and
a continuous process arrangement, possibly under autogeneous pressure built up, whereby the reactants are continuously injected into the reaction mixture and the phosphonic acid reaction product is withdrawn on a continuous basis.
9. The method in accordance with claim 1 wherein the amine is selected from the group of:
ammonia;
primary and secondary amines containing individual hydrocarbon groups having from 1 to 100 carbon atoms, said hydrocarbon moieties being represented by straight or branched linear alkyl moieties or cyclic alkyl moieties or aromatic or polyaromatic moieties or combinations thereof;
polyamines; and
primary and secondary amines or polyamines containing alkoxylated or thioalkoxylated radicals andor functional groups including trialkyl silyl, hydroxyl, carboxylic acid or sulfonic acid or esters of such acids or combinations thereof.
10. The method in accordance with claim 9 wherein the alkylamine is selected from methylamine, ethylamine, butylamine, octylamine, decylamine, dodecylamine, stearylamine, dimethylamine, diethylamine, dibutylamine, naphthylamine, benzylamine, aniline and cyclohexylamine.
11. The method in accordance with claims 1 and 7 wherein the acid catalyst has a pKa equal or inferior to 2.75.
12. The method in accordance with claim 1 wherein the phosphorous acid reactant is prepared, in a known manner, under substantial exclusion of halogen.
13. The method in accordance with claim 12 wherein the phosphorous acid is prepared, under substantial exclusion of halogen:
(i) by contacting elemental phosphorus with water at a temperature below 200\xb0 C. in the presence of a catalyst effective to promote oxidation of phosphorus by reaction with water; or
(ii) by contacting P(V) species with a reducing agent such as hydrogen in the presence of a reducing catalyst; or
(iii) by contacting a hydrolysis feed mixture comprising phosphite esters and phosphate esters with liquid water and steam to thereby hydrolyze the phosphite esters to phosphorous acid.
14. The method in accordance with claim 13 wherein the elemental phosphorus is tetraphosphorus.
15. The method in accordance with claims 1 and 9 wherein the polyamine is selected from the group of ethylene diamine, diethylene triamine, triethylene tetra-amine, di(propylene)ethylene tetra-amine, di(hexamethylene) triamine, hexamethylene diamine, polyethylene imine and polyallylamine.
16. The method in accordance with claim 1 wherein the phosphorous acid is prepared by reacting phosphorus trichloride with a reagent from the group of: a carboxylic acid; a sulfonic acid; and an alcohol followed by eliminating the chlorine containing products formed and the non-reacted raw materials by distillation or phase separation.
17. The method in accordance with claim 16 wherein chlorine containing products are eliminated to a level of 2000 parts-per-million (ppm) or smaller, expressed in relation to the level of the phosphorous acid component (100%)
18. The method in accordance with claim 1 wherein the phosphorous acid is prepared by hydrolyzing phosphorus trichloride followed by the substantial elimination of hydrochloric acid and other chloride intermediates originating from the hydrolysis.
19. The method in accordance with claim 18 wherein the hydrochloric acid and the chloride intermediates are eliminated to a level of. 2000 ppm of phosphorous acid component (100%).
20. The method in accordance with claim 1 wherein the acid catalyst has a pKa inferior to 1.9.
21. The method in accordance with claim 9 wherein the individual hydrocarbon groups in the primary and secondary amines have from 1 to 50 carbon atoms.
The claims below are in addition to those above.
All refrences to claim(s) which appear below refer to the numbering after this setence.
1. A tampon adapted to deliver a therapeutic agent to a tampon user, the tampon comprising:
a tampon body, wherein the tampon body is manufactured at a first manufacturing facility; and
a separate dosage form adapted to be coupled to the body, wherein the dosage form is not substantially liquefied when coupled to the tampon, wherein the dosage form includes a formulation including a therapeutic agent, wherein the dosage form is manufactured at a second manufacturing facility, wherein the dosage form and the tampon body are adapted to be sold separately to the tampon user, and wherein the tampon body and the dosage form are adapted such that the tampon user can attach the dosage form directly to the tampon body by partially melting the dosage form.
2. The tampon of claim 1, wherein partially melted dosage form partially absorbs into the tampon body.
3. The tampon of claim 1, wherein the dosage form is partially melted by heating the tampon body, and wherein the dosage form is attached to the tampon body by the tampon user contacting the dosage form with the tampon body.
4. A tampon adapted to deliver a therapeutic agent to a tampon user, the tampon comprising:
a tampon body, wherein the tampon body is manufactured at a first manufacturing facility; and
a separate dosage form adapted to be coupled to the tampon body, wherein the dosage form is not a film coating, wherein the dosage form includes a formulation including a therapeutic agent, wherein the dosage form is manufactured at a second manufacturing facility, wherein the dosage form and the tampon body are adapted to be sold separately to the tampon user, and wherein the tampon body and the dosage form are adapted such that the tampon user can attach the dosage form directly to the tampon body using a biologically-compatible adhesive.
5. The tampon of claim 4, wherein the dosage form includes the biologically-compatible adhesive, and wherein the biologically-compatible adhesive is protected by a covering.
6. A method for producing a medicated tampon for use by a tampon user, the method comprising:
manufacturing a tampon body at a first manufacturing facility;
manufacturing a dosage form at a second manufacturing facility, wherein the dosage form includes a formulation including a therapeutic agent;
providing the tampon body to the tampon user,
providing the dosage form to the tampon user; and
coupling the dosage form to the tampon body, wherein the coupling act is performed by the tampon user including partially melting the dosage form.
7. The method of claim 6, wherein the coupling act includes heating the tampon body, and contacting the dosage form with the tampon body to partially melt the dosage form.
8. A method for producing a medicated tampon for use by a tampon user, the method comprising:
manufacturing a tampon body at a first manufacturing facility;
manufacturing a dosage form at a second manufacturing facility, wherein the dosage form includes a formulation including a therapeutic agent;
providing the tampon body to the tampon user;
providing the dosage form to the tampon user; and
coupling the dosage form to the tampon body, wherein the coupling act is performed by the tampon user including affixing the dosage form to the tampon body using a biologically-compatible adhesive.
9. The method of claim 8, wherein the coupling act includes removing a protective covering from the biologically-compatible adhesive.
10. A method of making a medicated tampon for use by a tampon user, the method comprising:
providing a tampon;
procuring a dosage form comprising a dose of a therapeutic agent; and
providing the dosage form and the tampon to a tampon user, wherein the dosage form and the tampon are adapted such that the tampon user can attach the dosage form directly to the tampon body.
11. The method of claim 10, wherein the dose of the therapeutic agent remains substantially unchanged.
12. The method of claim 10, wherein the dosage form is attached to the tampon by partially melting the dosage form.
13. The method of claim 10, wherein the dosage form is attached to the tampon using a biologically-compatible adhesive.
14. The method of claim 10, wherein the tampon includes a tampon body, and wherein the dosage form is attached to the tampon by heating the tampon body and contacting the dosage form with the tampon body to partially melt the dosage form.
15. The method of claim 14, wherein a portion of the dosage form remains substantially intact.
16. The method of claim 14, wherein the dosage form is not substantially liquefied when coupled to the tampon.
17. The method of claim 14, wherein the tampon includes a distal end, and wherein the dosage form is positioned at the distal end of the tampon.
18. A method of making a medicated tampon for use by a tampon user, the method comprising the steps of:
providing a tampon;
procuring a dosage form comprising a dose of a therapeutic agent; and
providing the dosage form and the tampon to a tampon user, wherein the dosage form and the tampon are adapted such that the tampon user can place the dosage form adjacent to the tampon within a tube.
19. The method of claim 18, wherein the dosage form remains substantially intact.
20. The method of claim 18, wherein the tampon includes a distal end, and wherein the dosage form is placed at the distal end of the tampon.
21. A tampon adapted to deliver a therapeutic agent to a tampon user, the tampon comprising:
a tampon body; and
a dosage form adapted to be coupled to the body;
wherein the dosage form comprises a shape selected from the group consisting of a tablet, capsule, suppository, disk, and lozenge;
wherein the dosage form includes a formulation including a therapeutic agent; and
wherein the tampon body and the dosage form are adapted such that the tampon user can attach the dosage form directly to the tampon body by partially melting the dosage form.