United States Patent:  5,942,237

Assignee:  Lyfjathroun H.F. (Reykjavik, IS)

Filed:  October 6, 1995

A novel type of formulation for the topical administration of antigens and/or vaccines to mammals via mucosal membranes comprising one or more adjuvants/vehicles selected from (a) polyoxyethylene sorbitan monoesters, (b) polyoxyethylene castor oil, (c) caprylic/capric acid glycerides and (d) gangliosides in an amount of 0.01 to 15% (v/v) calculated on the total volume of the preparation. This formulation enhances the immunological response n a mammal following mucosal administration, e.g. nasal, oral, rectal or vaginal application.

Abstract of Description of the Invention

"The present invention presents a new and significantly improved method for the administration of antigens/vaccines, using the above new type of formulation. The method provides protective immune response in recipients of the antigen and/or the vaccine, both systemically and locally, which are elicited after intranasal immunization.

The primary object of the invention is to provide an intranasal composition, which is capable of producing a high systemic immune response (humoral and cellular, mainly of the IgG isotype) as well as locally produced antibodies of the secretory IgA isotype at mucosal surfaces without causing unacceptable damage to the nasal epithelial membrane.

It is another object of the invention to provide a controlled delivery system for intranasal application, which is biocompatible with the mucus and which is capable of dissolving required amounts of antigens and/or vaccines in small volumes.

According to an aspect of the invention the present delivery system is also usable for other mammalian surfaces such as the vagina, eye, mouth, lungs, ear, genital tract, gastrointestinal tract, rectum, skin etc.

As mentioned previously, the pharmaceutical preparation of the present invention is characterized by comprising one or more substances selected from

(a) polyoxyethylene sorbitan monoesters, (b) polyoxyethylene glycerol triesters, (c) caprylic/capric acid glycerides, and (d) gangliosides.

The preferred polyoxyethylene sorbitan monoester (a) is Polysorbate 20, which is a laurate ester of sorbitol and its anhydrides copolymerized with approximately 20 moles of ethylene oxide for each mole of sorbitol and sorbitol anhydrides.

The polyoxyethylene glycol triester (b) is preferably Polyoxyl-35-castor oil. This compound is mainly the triricinoleate ester of ethoxylated (about 35 moles) glycerol with smaller amounts of polyethylene glycol ricinoleate and the corresponding free glycols. Polyoxyl-35-castor oil is commonly known as Cremophor EL.

The caprylic/capric acid glycerides (c) are principally a mixture of mono-, di- and triglycerides in which the acid groups are only caprylic and capric acid groups. They are known commercially under the trade name Imwitor.

The gangliosides (d) of the above formula IV are principally a mixture of asialo-, monosialo-, disialo- and trisialogangliosides."

Claim 1 of 20 Claims

1. A pharmaceutical preparation for topical administration of antigens, vaccines, or both to mammals via a mucosal membrane, the preparation consisting essentially /of:

(a) a polyoxyethylene sorbitan monoester (PS) of the general formula: 

wherein R is laureate, palmitate, stearate or oleate; and each of w, x, y and z is independently 1 or 2; or each of w, x, y, z is independently less than or equal to 17 and the sum of w, x, y and z is 20;

(b) a mixture of mono-, di-, and triglycerides of a caprylic acid, a capric acid, or both (CCG) having the general formula:

 wherein each R¹ independently is H or a C₈ -C₁₀  acyl group, provided that at least one R.sup.1 is a C₈ -C₁₀  acyl group; and

(c) water, an aqueous buffer, an antigen, or a combination thereof;

wherein, the CCG and PS are present at respective concentrations of 0.01% to 24% CCG and 0.1% PS to 57.5% PS, each percentage being (v/v) and the preparation containing more PS than CCG and more water or aqueous buffer than oil.

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