High frequency application of botulinum toxin therapy

Abstract

The present invention relates to methods for treating diseases and disorders by administering a composition containing the neurotoxic component of a Clostridium botulinum toxin complex, wherein the composition is devoid of any other protein of the Clostridium botulinum toxin complex and wherein the composition is administered at short intervals and/or in high doses.

Claims

1. A method of treating a disease or condition caused by or associated with hyperactive cholinergic innervation of exocrine glands in a patient, the method comprising administering a composition comprising a therapeutically effective amount of a neurotoxic component of a Clostridium botulinum toxin complex, the composition being devoid of any other protein component of the Clostridium botulinum toxin complex, to remove partially or completely the treated disease or condition symptoms, wherein (a) the patient is a human, (b) the composition is locally administered by injection of a non-lethal dose to an exocrine gland exhibiting hyperactive cholinergic innervation, and (c) the composition is administered at an interval that provides a stable quality of life for the patient, the interval comprising a first treatment and a second treatment, wherein the second treatment is carried out at a point in time when the efficacy of the first treatment begins to decline.

2. The method of claim 1, wherein the second treatment is performed in order to improve the treatment effect of the first treatment.

3. The method of claim 1, wherein the patient is a human, who has been treated with a Clostridium botulinum toxin but who complains about a decrease of the treatment effect and who requires an additional treatment within 3 months of a previous treatment.

4. The method of claim 1, wherein the hyperactive gland is an autonomic exocrine gland and wherein the composition is injected into or in the vicinity of such gland.

5. The method of claim 4, wherein the (a) gland is selected from the group consisting of sweat glands, tear glands, salivary glands and mucosal glands; or (b) gland is associated with a disease or condition selected from the group consisting of Frey syndrome, Crocodile Tears syndrome, axillar hyperhidrosis, palmar hyperhidrosis, plantar hyperhidrosis, hyperhidrosis of the head and neck, hyperhidrosis of the body, rhinorrhea, or relative hypersalivation in patients with stroke, Parkinson's disease or Amyotrophic Lateral Sclerosis.

6. The method of claim 1, wherein the neurotoxic component is selected from the group consisting of type A, B, C, D, E, F, G or a mixture thereof.

7. A method of treating a disease or condition caused by or associated with hyperactive cholinergic innervation of exocrine glands in a patient, the method comprising administering a composition comprising a therapeutically effective amount of a neurotoxic component of a Clostridium botulinum toxin complex, to remove partially or completely the treated disease or condition symptoms, wherein (a) the patient is a human, (b) the composition is locally administered by injection of a non-lethal dose to an exocrine gland exhibiting hyperactive cholinergic innervation, and (c) the composition is administered at an interval that provides a stable quality of life for the patient, the interval comprising a first treatment and a second treatment, wherein the second treatment is carried out at a point in time when the efficacy of the first treatment begins to decline.

Description

EXAMPLE 1

Botulinum Toxin Therapy for Treatment of Cervical Dystonia

(1) A 45 year-old male patient suffering from cervical dystonia is evaluated for botulinum toxin therapy. After all appropriate examinations an injection scheme is constructed and botulinum toxin free of complexing proteins is applied accordingly in a total dose of 300 MU. On re-evaluation after 2 weeks the symptomatology is improved, but there is a need to include additional target muscles and to increase the botulinum toxin dose in initially injected target muscles. Two weeks later the patient is re-evaluated again and the treatment result is optimal.

(2) Adverse effects do not occur. So far, on 7 subsequent injection series the treatment results are maintained without any indication of antibody-induced therapy failure.

EXAMPLE 2

Botulinum Toxin Therapy for Treatment of Blepharospasm. Short Duration of Action

(3) A 61 year-old female patient suffering from blepharopsasm is treated with a medicament containing the neurotoxic component of the present invention, free of complexing proteins, in a total dose of 48 MU with excellent results. 4 weeks after the injections with the neurotoxic component the effect begins to wane. After 2 more weeks the effect of the treatment has almost completely ceased. Re-Injections are performed 7 weeks after the initial injection series. Therapy with the neurotoxic component is repeated in the initial dose and with identical effects. Therapy with the neurotoxic component is continued for 6 subsequent injection series with excellent therapeutic results and without any indication of antibody-induced therapy failure.

EXAMPLE 3

Botulinum Toxin Therapy for Treatment of Generalised Spasticity

High Dose Application

(4) A 35 year-old male patient suffering from hypoxic brain damage with generalized spasticity. The neurotoxic component of the present invention, free of complexing proteins in a total dose of 750 MU, is administered in three aliquots of 250 MU given with 1 day intervals. 2 weeks after the application the condition has improved substantially. Adverse effects, neither local nor regional nor systemic, cannot be detected. On 7 subsequent injection series the therapeutic effect is stable without occurrence of adverse effects. There is no indication of antibody-induced therapy failure.

EXAMPLE 4

Cosmetic Use of Botulinum Toxin. Difficulties in Constructing the Injection Scheme and Short Duration of Action

(5) A 40 year old female client presenting with muscular frowning lines and horizontal frontal lines was treated with 20 MU of botulinum toxin free of complexing proteins (i.e. the neurotoxic component of the present invention). 2 weeks later there is an improvement of the symptomatology, but additional injection of 20 MU of botulinum toxin are necessary. 2 weeks later the outcome is fully satisfactory for the patient. 4 weeks later the favorable effect starts to wane, so that botulinum toxin re-injections in a total dose of 40 MU become necessary. So far, the client has undergone 4 subsequent injection series with total doses of 40 MU each. There is no indication of antibody-induced therapy failure.