Mixture of hyaluronic acid for treating and preventing peptic ulcer and duodenal ulcer
Inventors
Assignees
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Publication Number
US-8722644-B2
Publication Date
2014-05-13
Expiration Date
Abstract
The present invention is related to a method of treating and preventing peptic ulcer and duodenal ulcer by administering hyaluronic acid composition with a binary mixture of hyaluronic acids having mainly different weight-average molecular weight and then different rheological, scaffold and degradation properties in aqueous solution. The resulted compositions have demonstrated an optimal balance between adhesion, tissue scaffold and treating time to the peptic and duodenal ulcer and bleeding. Thus, the present inventive binary mixture exhibits a quick and lasting effect on the treatment and prevention of duodenal or peptic ulcer and bleeding.
Core Innovation
The invention provides a method to treat and prevent peptic ulcers and duodenal ulcers by administering a therapeutically effective amount of a hyaluronic acid mixture consisting essentially of a low average molecular weight hyaluronic acid (LMWHA) and a high average molecule weight hyaluronic acid (HMWHA). The LMWHA has an average molecular weight of 0.5 million Da and the HMWHA has an average Mw within 1.5 million to 3.5 million Da. The mixture has a defined mixing ratio of LMWHA and HMWHA by weight from 20:80 to 80:20.
The binary hyaluronic acid mixture is stated to balance rapid adhesion and tissue scaffold formation associated with LMWHA with a longer-lasting effect via natural degradation and compensation associated with HMWHA. The concept relies on the differing molecular weights of LMWHA and HMWHA to achieve both adhesion/scaffold behavior and persistence through natural degradation.
The disclosure further states that the binary hyaluronic acid mixture reduces bleeding and demonstrates activity in aspirin-induced ulcer contexts, including activity relevant to peptic ulcers and duodenal ulcers. Supporting evidence described includes separation/degradation behavior evaluated under HAase and acidic conditions using CE and GPC, and adhesion to injured colon tissue using fluorescently labeled HA and an IVIS colon tissue adhesion assay.
Claims Coverage
The independent claim covers a method for treating and preventing both peptic ulcers and duodenal ulcers using a binary hyaluronic acid mixture administered in a therapeutically effective amount. Two key inventive feature groups are present: the molecular-weight-defined LMWHA/HMWHA mixture and the LMWHA:HMWHA weight mixing ratio within a defined range.
Therapeutically effective LMWHA/HMWHA binary mixture for ulcer treatment
A method for treating and preventing peptic ulcers and duodenal ulcers comprising administering to a subject a therapeutically effective amount of a hyaluronic acid mixture consisting essentially of a low average molecular weight hyaluronic acid (LMWHA) and a high average molecule weight hyaluronic acid (HMWHA), wherein the average molecular weight (Mw) of LMWHA is 0.5 million Da and the average Mw of HMWHA is within 1.5 million to 3.5 million Da.
Defined LMWHA:HMWHA weight mixing ratio range
The method wherein the mixing ratio of the LMWHA and the HMWHA is in a range from 20:80 to 80:20 by weight.
Equal 1:1 LMWHA to HMWHA mixing ratio
The method of claim 1 further comprises a 1:1 mixing ratio of LMWHA and HMWHA.
Concentration range in PBS or pharmaceutical buffer solution
The method of claim 1 further specifies that the hyaluronic acid mixture is prepared at a concentration range of 0.5 mg/ml to 10 mg/ml in phosphate buffered saline (PBS) or a pharmaceutical buffer solution.
Oral solid dosage form or oral/injection solution with oral or endoscope injection
The method of claim 1 is further defined such that the hyaluronic acid mixture contains an excipient to produce an oral solid dosage form or an oral/injection solution, and the administration is by oral administration or endoscope injection.
Use with selected adjuvants to potentiate drug effect
A method described in which a hyaluronic acid mixture is used together with a selected adjuvant—coagulant, antacid, H2 blocker, potassium hydrogen ion pump blocker, or mucosa protector—to potentiate the drug effect.
Treatment and prevention of ulcer-associated bleeding
The method of claim 1 further uses a hyaluronic acid mixture to treat and prevent bleeding associated with a peptic ulcer or duodenal ulcer.
Overall, the claims focus on administering a binary hyaluronic acid mixture consisting essentially of LMWHA and HMWHA with defined molecular weight characteristics and a specified LMWHA:HMWHA by-weight mixing ratio (20:80 to 80:20). Dependent claims refine the mixing ratio, specify preparation concentration in PBS or pharmaceutical buffer solution, define formulation and administration routes, introduce use with adjuvant categories, and extend the target to preventing and treating ulcer-associated bleeding.
Stated Advantages
Reduces bleeding.
Balances rapid adhesion and tissue scaffold formation with longer-lasting effect via natural degradation/compensation.
Demonstrates activity in aspirin-induced ulcer contexts.
Documented Applications
Treating and preventing peptic ulcers and duodenal ulcers in a subject.
Treating and preventing bleeding associated with a peptic ulcer or duodenal ulcer.
Activity demonstrated in an aspirin-induced ulcer rat model (PU98), including weight-based amelioration outcomes.
Assessment of adhesion to injured colon tissue using fluorescently labeled HA and an IVIS colon tissue adhesion assay.
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