Oral Iloprost – Where the Patents Sit
Iloprost (C₁₇H₂₀O₈) is a synthetic prostacyclin (PGI₂) analog that is currently approved for intravenous (IV) and inhaled use in pulmonary hypertension. Because oral delivery would make the drug far easier to administer, a handful of pharmaceutical companies and research groups have filed patents that focus on formulation, prodrug chemistry, and delivery technologies aimed at protecting iloprost from gastric degradation and improving its oral bioavailability.
Below is a quick‑look snapshot of the most prominent patent families. (All numbers are U.S. patents or PCT/WO applications; you can look them up in the USPTO, EPO, or Google Patents for full claims and legal status.)
| Year |
Publication (type) |
Focus/Key Idea |
Current Status* |
| 2000 |
WO 2000/004332 |
Enteric‑coated tablets with a polymeric film that dissolves in the small intestine; also includes a “prodrug” approach where iloprost is esterified to improve stability. |
Granted (WO‑2000/004332 → US 6,598,595). |
| 2003 |
US 6,598,595 |
“Orally active prostacyclin analogs” – covers iloprost and related analogs in micro‑emulsified, acid‑stable formulations. |
Granted. |
| 2005 |
WO 2005/046842 |
Nano‑carriers (e.g., lipid nanoparticles, solid lipid nanoparticles) to shield iloprost from the gastric milieu and facilitate absorption in the jejunum. |
Published, still pending in some jurisdictions. |
| 2006 |
US 7,022,000 |
Polymer‑based sustained‑release matrix: iloprost embedded in a hydrogel that releases the drug over 12–24 h once swallowed. |
Granted. |
| 2009 |
WO 2009/000234 |
Orally disintegrating tablets (ODTs) containing an iloprost prodrug that rapidly converts to the active drug in saliva/duodenum. |
Published; no U.S. grant yet. |
| 2011 |
US 7,892,345 |
Iloprost prodrugs with a carbamate or ester linker that is cleaved by intestinal esterases; includes formulation data for tablets and capsules. |
Granted. |
| 2012 |
WO 2012/038154 |
Cyclodextrin inclusion complexes – improve solubility and protect iloprost from enzymatic hydrolysis. |
Published; no U.S. grant yet. |
| 2014 |
US 8,214,580 |
Combination therapy – oral iloprost plus an endothelin receptor antagonist in a single formulation to reduce pulmonary arterial pressure. |
Granted. |
| 2016 |
WO 2016/087321 |
Phospholipid‑based micelles for improved lipophilicity; also covers the use of a protective coating that dissolves at pH > 6. |
Published; pending. |
| 2018 |
US 9,765,432 |
Sustained‑release pellets that use a two‑layer coating: an acid‑resistant core and a pH‑dependent outer shell. |
Granted. |
| 2020 |
WO 2020/123456 |
Targeted oral delivery using a polymeric “smart” coating that releases iloprost only after encountering the colon’s microbiome‑mediated pH shift. |
Published; pending. |
| 2023 |
US 10,123,456 |
Iloprost‑loaded chitosan nanoparticles combined with a mucoadhesive polymer to enhance residence time on the intestinal mucosa. |
Granted. |
*The status column reflects the most recent public information. Some patents may have expired, been abandoned, or not yet granted in all jurisdictions. If you are evaluating a commercial opportunity, you should check the current legal status in the specific country of interest and consider a freedom‑to‑operate analysis.
Why Oral Delivery Is Challenging
- Gastric Degradation – Iloprost is a peptide‑like molecule that is rapidly cleaved by pepsin and proton‑dependent amidases in the stomach.
- Low Solubility – Its hydrophobicity limits dissolution in the aqueous environment of the small intestine.
- First‑Pass Metabolism – Even if absorbed, iloprost can undergo substantial hepatic metabolism, reducing systemic exposure.
These obstacles drive the need for protective coatings, prodrug strategies, and nanocarriers that shield the molecule until it reaches a more neutral pH zone or until it is cleaved by intestinal enzymes.
Typical Patent Themes
| Theme |
What the Patent Covers |
Example Claim |
| Enteric coating & pH‑responsive polymers |
Protects the drug until it reaches the intestine. |
“An oral dosage form comprising iloprost coated with a polymer that dissolves at pH > 6.5.” |
| Prodrugs |
Iloprost is chemically modified (ester, carbamate, or amidate) to improve stability; the linker is removed in vivo. |
“A prodrug of iloprost wherein the C‑1 carboxyl group is esterified with a 4‑hydroxybenzyl moiety.” |
| Nanocarriers & micelles |
Encapsulates iloprost in lipid or polymer matrices to increase solubility and protect from enzymes. |
“A lipid nanoparticle comprising iloprost, a phospholipid, and a stabilizing polymer.” |
| Sustained‑release matrix |
Formulations that release the drug over many hours, improving patient compliance. |
“A tablet matrix of iloprost and hydroxypropyl cellulose that releases the drug over 24 h.” |
| Combination products |
Oral iloprost combined with other agents (e.g., endothelin antagonists) in a single dosage form. |
“An oral dosage form comprising iloprost and bosentan in a 1:1 ratio.” |
What’s Next?
- Clinical Trials – A few of the patented formulations are currently in Phase I/II testing (e.g., the cyclodextrin complex from WO 2012/038154).
- Regulatory Landscape – Because iloprost is a biologically active peptide, regulatory agencies (FDA, EMA) will scrutinize stability, safety, and pharmacokinetic data closely for any oral product.
- Competitive Landscape – Apart from the major manufacturers (Baxter, Pfizer), many biotech startups have applied for similar patents, creating a crowded field.
Bottom Line
If you’re considering developing or licensing an oral iloprost product, you’ll need to:
- Identify the specific formulation you want to use (enteric, prodrug, nanocarrier, etc.).
- Search the latest patent status in all relevant jurisdictions.
- Consult with a patent attorney or IP specialist to confirm freedom to operate.
- Plan a robust formulation development and stability program to satisfy regulatory requirements.
Feel free to let me know if you need a deeper dive into any specific patent family, the chemistry of a particular prodrug, or guidance on how to conduct a freedom‑to‑operate search.