WO1993002700A1 - Use of collagen for the prophylaxis of herpes labialis infections - Google Patents

Abstract

The invention concerns the use of collagen to prepare a drug for the prophylaxis of $i(Herpes Labialis) infections. In a preferred embodiment, an injection suspension containing collagen and, optionally, a local anaesthetic is prepared. It is administered by injection into the transition zone between the skin and the mucous membrane in the lip area.

Description

 Use of collagen for prophylaxis of labial herpes infections

The invention relates to the use of collagen for the prophylaxis of labial herpes infections.

Various skin and mucous membrane diseases are summarized under the term herpes in humans. An example of this is blister lichen, herpes simplex, a virus-related, harmless skin condition in which grouped, millet-sized blisters, for example, appear on the mouth (herpes labialis), which dry up after a few days. It shows up in febrile illnesses (especially with pneumonia or kidney infections or malaria), after heavy tanning and in women during menstruation.

So far, no drugs are known that can prevent the occurrence of herpes labialis prophylactically.

The therapy of labial herpes has so far been carried out by labial application of vitamin C or antivirals (iodine deoxyuridine) or, under certain circumstances, also by systematic administration of acyclovir (Zovirax), which inhibits virus duplication. These agents limit the herpes labialis infection, but the appearance of vesicular lichen can never be completely prevented. In order to be able to successfully isolate the infection, it is also necessary to always have the appropriate therapeutic agent at hand, as late application is ineffective.

Collagens are long-fiber, linear-colloidal, high-molecular Skieroproteins of the extracellular matrix, which occur in connective tissues (e.g. skin, cartilage, tendons, ligaments and blood vessels), in the protein-containing basic substance of the bone (ossein) and in dentin (dentin) together with proteoglycans. With a share of 25 to 30%, they are the most common animal proteins in terms of quantity. The basic structural unit of collagen, tropo-collagen (MW approx. 300,000), consists of three polypeptide chains in the form of special left-handed helices, which - in accordance with a technique also known in rope making - are in turn turned to the right (triple helix). The tropo-collagen molecule is a "rope" of 280 nm in length with a diameter of 1.4 nm; the fibrils measure a cross-section of 200-500 nm (see Römpps Chemielexikon, Vol. 3, p. 2297, 1990).

In contrast to most proteins in the animal body, the collagens are not continuously renewed. Once formed, they no longer participate in metabolism and age due to the regular increase in crosslinking due to the formation of hydrogen bonds, ester bonds of amino acid and sugar residues and isopeptide bonds between elongated amino acid chains.

Modified collagen is being tested in medicine as a temporary skin replacement, as a replacement for cornea and vitreous fluid in the eye, as a replacement for tendons, tendon sheaths, hollow organs and veins, as a blood plasma substitute and in wound healing (EP-B 52288, .TP-A-52 -076416). Collagen sponge is used as a hemostatic agent. Medicines containing collagen are used to improve expandable skin deformations, such as those associated with scars, skin loss caused by different causes, and age-related skin folds. These collagen-containing medicines are injected under the skin to be filled in and for this reason usually contain a local anesthetic.

The object of the present invention is to produce a medicament for the prophylaxis of herpes labialis infections.

This object is achieved in that collagen is used for the manufacture of a medicament for the prophylaxis of herpes labialis infections.

The collagen used is insoluble collagen, which can be obtained from calf or bovine skin, for example; however, collagen from bovine skin is preferred.

The collagen is preferably in the form of an injection suspension, particularly preferably in an amount of about 20 to 50 mg / ml. The suspension for injection is applied in particular by injection into the skin-mucous membrane transition in the mouth area. For this reason, a local anesthetic, such as bupivacaine or lidocaine, is preferably included. Lidocaine is particularly preferably contained in the injection suspension. The preferred amount of local anesthetic contained is 1-5 mg / ml.

Compared to the previous options, introducing collagen into the skin-mucous membrane transition in the mouth area has the advantage that the occurrence of herpes efflorescence can be prevented prophylactically.

The following examples illustrate the invention. Examples up to 5

The following examples show different compositions of the active ingredient combination in the injection suspension:

1 ml suspension for injection containing:

1. 20 mg collagen from calf skin

2 mg bupivacaine;

2. 30 mg collagen from bovine skin

2 mg bupivacaine;

3. 35 mg collagen from bovine skin

3 mg lidocaine;

4. 40 mg collagen from bovine skin

3 mg lidocaine;

5. 50 mg collagen from calf skin 3.5 mg bupivacaine.

Application example l

It was observed in one patient that even two years after infiltration of the collagen-containing injection suspension according to Example 3, her labial herpes, which had previously been very strong and regular, no longer occurred in the lip area. When the injection was repeated for cosmetic reasons, no herpes labialis could be observed since then (11/2 years).

Two further patient results were available over a symptom-free period of 2 1/2 and 3 1/2 years. All treated patients regularly had labial herpes infections before treatment. These generally occurred when the sun was more intense, for example when skiing, together with minor infections. The patients were also exposed to these influences after treatment. The accompanying herpes labialis infections no longer occurred after the treatment.

Further results are available from seven patients who were treated about half a year ago. No infection was found in these patients during the observation period. Before treatment, these patients were very regularly and severely affected by herpes labialis.

Claims

Claims 1. Use of collagen for the manufacture of a medicament for the prophylaxis of; herpes labialis infections. 2. Use according to claim 1, characterized in that the collagen is contained in an injection suspension. 3. Use according to claim 2, characterized in that the amount of collagen contained in the injection suspension is about 20-50 mg / ml. 4. Use according to one of claims 1 to 3, ^" characterized in that a local anesthetic is also contained. 5. Use according to claim 4, characterized in that the amount of local anesthetic contained in the injection suspension is 1-5 mg / ml. 6. Use according to one of claims 1 to 5, characterized in that the collagen contained in the medicinal product is collagen from bovine skin.