Applications for μco™ System

For Absorption

Great drug absorption is reached through the nasal mucosa due to a dense microvascular network.
The nasal route is beneficial for any treatment requiring fast onset of action bypassing first-pass metabolism, or treatments required for patients with difficulty swallowing oral medication.

For Vaccination

Vaccines applied to the nasal mucosa produce mucosal antibodies.
When upper respiratory tract infections occur, including those in the nasal mucous membrane, mucosal antibodies contribute to first-line defense before the virus invades the internal system.

For Nose-to-Brain

Drug delivery directly from the olfactory region to the brain can be identified.
For drugs do not or difficult to pass the blood-brain barrier (BBB), nasal would be an ideal route for the delivery to the brain.

Absorption
Vaccination
Nose-to-Brain

Nasal Application of Systemic Drugs

Benefits of Nasal Application

Increased nasal absorption

Rapid absorption: beneficial for emergency treatment and acute symptoms (pain relief, etc.)
Improved bioavailability: beneficial for drugs undergoing significant first-pass metabolism and drugs susceptible to degradation in the GI tract (e.g. peptides)

Needle-free doing (non-invasive)

The needleless device is easy-to-use and carries no potential risks of pain or accidents with needle injections (beneficial for replacement of injections.)

Increased stability of formulations

The powder formulation is expected to extend the stability at room temperature due to dry powder.

Alternative administration route for patients with difficulties in swallowing

More reliable administration route for diseases and conditions where patients’ swallowing abilities are impaired (Nausea and vomiting, motion sickness, morning sickness, migraine, anaphylaxis, etc.)

Therapeutic Areas Suitable for μco™ System

μco™ System is an innovative nasal delivery platform technology improving rapid drug on-set and bioavailability. These advantages of nasal administration are maximized at the following therapeutic area.

Post-operative pain, breakthrough cancer pain, migraine
Epilepsy, convulsion
Sedation
Insomnia
Nausea, vomiting
Abdominal pain
Anaphylaxis
Endocrine disease (peptide drug treatment for diabetes and central diabetes insipidus or peptide drug prevention of postpartum hemorrhage)
Gynecology (peptide drug treatment for infertility and menopausal symptom)

Small Molecules
Peptides

Nasal Application of Systemic Drugs - Small Molecules

Small Molecule Properties Affecting Absorption

When used with the μco™ System, the active pharmaceutical ingredient (API) first dissolves in the nasal mucus and then permeates through the nasal epithelium into the blood stream. For small molecular APIs, the key factors for high absorption are solubility, molecular weight, and lipophilicity (LogP).

Physical Properties of Small Molecules Applicable to μco™ System

The figures show the relationship between bioavailability of APIs combined with the μco™ System and their molecular weights and lipophilicity (LogP), respectively, according to the results of studies using non-human primates.

The results above show that the μco™ System achieves high absorption (over 50% BA in non-human primates) for APIs with the properties listed below.

Molecular weight < 600
LogP > 0
Appropriate water solubility for the intended clinical dose

Example using μco™ System (small molecule)

Nasal Zolmitriptan for Migraine

Rapid pain relief is crucial for migraine patients.
In a Phase I study conducted in the US, nasal zolmitriptan using the μco™ System showed a rapid increase in blood concentration immediately after dosing. This was faster and resulted in higher absorption when compared with a marketed nasal liquid spray. The bioavailability of the first 10 minutes was 12-fold that of the marketed nasal liquid spray.

Nasal Application of Systemic Drugs - Peptides

Peptide Properties Affecting Absorption

When used with the μco™, the active pharmaceutical ingredient (API) first dissolves in the nasal mucus and then permeates through the nasal epithelium into the blood stream. For peptides, absorption is generally dependent only on the molecular weight, as permeation of peptides through the nasal epithelium tends to be the limiting process for absorption.

Physical Properties of Peptides Applicable to μco™ System

Figure shows the relationship between bioavailability of various peptides when delivered using μco™ System and its molecular weight.

In general, μco™ System can achieve high absorption for peptide with molecular weight less than 6,000.

Example using μco™ System (peptide)

Nasal Calcitonin for Treatment of Osteoporosis

Therapy without the use of needles is primary in patient using peptide drugs.
In a pharmacokinetic study in non-human primates, nasal calcitonin using the μco™ System showed a rapid increase in blood concentration immediately after dosing with a significantly higher absorption when compared with a marketed nasal liquid spray. The bioavailability in the first 10 minutes was 16-fold that of the marketed nasal liquid spray.

Nasal Application of Vaccines

Advantages of Nasal Application of Vaccines

Prevention of viral infections with mucosal immunity (first line of defense)
Prevention of viral replication in the body even after infection (second line of defense)
Protection against viral mutant strains, possible with mucosal immunity
Painless, needle-free administration
Extended stability at room temperature with powder formulation (“cold chain free”)

従来型の注射ワクチンは、皮下に注射することにより、血液中に産出された抗体(lgG)が、体内に侵入したウイルスの増殖を防御する効果がありますが、ウイルスのタイプが変わると防御能が低くなるというデメリットも持ち合わせています。対して経鼻ワクチンは、針なしでワクチンを経鼻投与することができ、粘膜免疫機構を活性化させ、鼻粘膜から分泌される抗体（slgA）を産出させることにより、ウイルスの侵入を鼻腔内で防御するため、ウイルスのタイプが変わっても高い防御能を有します。

Indications for candidate vaccines using μco™ System

Viral respiratory infections such as seasonal / pandemic Flu and RSV
Viral mucosal infections such as HPV

Example using μco™ System (Vaccines)

Pre-clinical Results of Nasal Flu Vaccine

Nasal flu vaccines using the μco™ System provide effective production of mucosal immunity defending against flu virus infection at the site of entry before the virus enters the body. Additional advantages include cross-protection and needle-free dosing with greater stability at room temperature when compared with a liquid formulation.
In an immunogenicity study in non-human primates, a flu vaccine using the μco™ System showed greater sIgA production in the mucosal membrane when compared with an injection and a nasal liquid spray. Flu vaccine with the μco™ System induced 4-fold the sIgA production when compared with the nasal liquid spray.

Nose-to-Brain

Advantages of Nasal Application for Nose-to-Brain Delivery

Enhanced delivery of drugs to the brain that may show difficulty in penetrating the blood-brain-barrier (BBB)
Reduced number of adverse effects resulting from systemic exposure of the drug
A more patient-friendly option when compared with invasive delivery routes such as intrathecal injection

Therapeutic Areas Suitable for Nose-to-Brain Technology

Central nervous system diseases (e.g. Alzheimer’ s disease, Parkinson’ s disease, brain tumor, etc.)

Example using μco™ System （Nose-to-Brain）

Pre-clinical studies of drug delivery targeting the olfactory region

In an MRI imaging study in non-human primates, animals were administered manganese containing formulation using a delivery device designed to target the olfactory region. The manganese was distributed solely in the olfactory region immediately following administration and reached the brain (olfactory bulb) 24 hours following administration.