JPWO2020186121A5

JPWO2020186121A5 -

Info

Publication number: JPWO2020186121A5
Application number: JP2021554738A
Authority: JP
Publication date: 2023-03-14

Description

７．調製物が、約１９．３～１９．９ＩＵのインスリンを含む、項目１に記載の調製物。 7. The preparation of item 1, wherein the preparation contains about 19.3-19.9 IU insulin.

３０．インスリンを含む治療用調製物であって、調製物は、経口摂取後に患者の腸壁または周囲組織への挿入に適合されており、挿入時に、調製物は、分解して、インスリンを腸壁または周囲組織から患者の血流に放出し、放出は、上昇部分および下降部分を有する血漿濃度プロファイルを示し、上昇部分が、下降部分でインスリンのＣ_ｍａｘレベルからインスリンの放出前レベルまで移行するのにかかる時間よりも、少なくとも約２倍速く、インスリンの放出前レベルからインスリンのＣｍａｘレベルに到達する、治療用調製物。 30. A therapeutic preparation comprising insulin, wherein the preparation is adapted for insertion into the intestinal wall or surrounding tissue of a patient after oral ingestion, wherein upon insertion the preparation degrades to release insulin into the intestinal wall or Released into the patient's blood stream from the surrounding tissue, the release exhibits a plasma concentration profile having a rising portion and a falling portion, with the rising portion transitioning from the _Cmax level of insulin to the pre- release level of insulin in the falling portion. A therapeutic preparation that reaches a Cmax level of insulin from a pre-release level of insulin at least about 2 times faster than such time.

３１．上昇部分が、下降部分でインスリンのＣ_ｍａｘレベルからインスリンの放出前レベルに移行するのにかかる時間よりも、約３～５倍速い範囲で、インスリンの放出前レベルからインスリンのＣ_ｍａｘレベルに到達する、項目３０に記載の調製物。 31. The C _max level of insulin is reached from the pre- release level of insulin to the C max level of insulin in the range of about 3-5 times faster than the time it takes for the rising portion to go from the C _max level of insulin to the pre-release level of insulin in the falling portion. 31. The preparation of item 30.

３２．上昇部分が、下降部分でインスリンのＣ_ｍａｘからインスリンの放出前レベルに移行するのにかかる時間よりも、約４．５倍速く、インスリンの放出前レベルからインスリンのＣ_ｍａｘレベルに到達する、項目３０に記載の調製物。 32. an item in which the ascending portion reaches a _Cmax level of insulin from a pre -release level of insulin approximately 4.5 times faster than the time it takes for the descending portion to go from _Cmax of insulin to a pre-release level of insulin; 30. The preparation according to 30.

３５．インスリンを患者に送達するための方法であって、
固体インスリン投与量を提供することと、経口摂取後、固体投与量インスリンを患者の腸壁または周囲組織に送達することであって、インスリンは、腸壁または周囲組織の固体投与量インスリンから患者の血流に放出されて、上昇部分および下降部分を有する血漿濃度プロファイルを生成し、上昇部分が、下降部分でインスリンのＣ_ｍａｘからインスリンの放出前レベルに移行するまでの時間よりも、少なくとも約２倍速く、インスリンの放出前レベルからインスリンのＣｍａｘレベルに到達する、送達することと、を含む、方法。 35. A method for delivering insulin to a patient, comprising:
providing a solid dose insulin and delivering the solid dose insulin to the intestinal wall or surrounding tissue of the patient after oral ingestion, wherein the insulin is transferred from the solid dose insulin in the intestinal wall or surrounding tissue to the patient. is released into the bloodstream to produce a plasma concentration profile having a rising portion and a falling portion, the rising portion being at least about 2 times longer than the time to transition from insulin C _max to the pre- release level of insulin in the falling portion reaching a Cmax level of insulin from a pre-release level of insulin twice as fast.

３６．上昇部分が、下降部分でインスリンのＣｍａｘレベルからインスリンの放出前レベルに移行するのにかかる時間よりも、約３～５倍速く、インスリンのＣ_ｍａｘレベルに到達する、項目３５に記載の方法。 36. 36. The method of item 35, wherein the rising portion reaches the Cmax level of insulin about 3-5 times faster than the time it takes to go from the _Cmax level of insulin to the pre- release level of insulin in the falling portion.

Claims

A therapeutic preparation comprising from about 19.3 IU to about 19.9 IU of insulin, said preparation being adapted for insertion into the wall or surrounding tissue of a patient's small intestine after oral ingestion, wherein upon insertion: The preparation degrades to release the insulin from the wall or surrounding tissue of the small intestine into the bloodstream of the patient , and the insulin in the preparation ranges from an insulin dose of about 381-527 pM/kg body weight/IU. A therapeutic preparation that provides a plasma concentration of

2. The preparation of claim 1 , wherein the insulin released into the patient's blood stream provides a relative bioavailability in the range of about 104-129% compared to subcutaneously injected doses of insulin.

2. The preparation of claim 1, wherein said insulin is human recombinant insulin.

2. The preparation of claim 1, wherein said insulin released into said patient's bloodstream results in an area under the insulin concentration curve of 65 nM/min to 101 nM/min.

2. The preparation of claim 1, wherein at least a portion of said preparation is in solid form.

2. The preparation of claim 1, wherein the preparation comprises biodegradable materials that degrade within the walls of the small intestine , releasing the insulin into the patient's bloodstream.

2. The preparation of claim 1, wherein the preparation comprises a tissue-piercing member configured to penetrate and be inserted into the lumen wall of the GI tract or surrounding tissue .

2. The formulation of claim 1, wherein the weight percent of insulin in said formulation ranges from about 2% to about 15%.

2. The preparation of claim 1, wherein the insulin released into the patient's blood stream provides a relative bioavailability in the range of about 72-129% compared to subcutaneously injected doses of insulin.

The insulin released into the bloodstream of said patient exhibits a plasma concentration profile having a rising portion and a falling portion, said rising portion transitioning from a _Cmax level of insulin to a pre- release level of insulin in said falling portion. 2. The preparation of claim 1 , wherein the _Cmax level of insulin is reached from the pre-release level of insulin at least about 2 times faster than the time taken to.

2. The formulation of claim 1, wherein the formulation is adapted for oral delivery in a swallowable capsule.

11. The preparation comprises at least one pharmaceutical excipient, optionally said at least one pharmaceutical excipient comprises at least one of a binder, a preservative, or a disintegrant. A preparation as described in .

Insulin delivery to a patient or use of insulin in a pharmaceutical preparation to treat diabetes or other glucose dysregulation, said pharmaceutical comprising about 19.3 IU to about 19.9 IU of insulin The medicament in the form of a solid insulin dose, wherein the medicament is adapted for insertion into the wall or surrounding tissue of the small intestine of a patient after oral ingestion, wherein the solid insulin dose in the wall or surrounding tissue of the small intestine is , releasing said insulin from the wall of said small intestine or surrounding tissue into said patient's blood stream, producing a plasma concentration of insulin in said dosage in the range of about 381-527 pM/kg body weight/IU.

The solid insulin dose exhibits a plasma concentration profile having an ascending portion and a descending portion, the ascending portion being the C of insulin in the descending portion. _ｍａｘmax said C of insulin from said pre-release level of insulin at least about twice as fast as the time it takes to transition from said level of insulin to said pre-release level of insulin _ｍａｘmax 14. Use according to claim 13, wherein insulin reaching a level is released into the patient's bloodstream.

14. Use according to claim 13, wherein insulin is released into the patient's bloodstream resulting in an area under the insulin concentration curve of 65 nM/min to 101 nM/min.

14. Use according to claim 13, wherein the weight percent of insulin in said solid insulin dose ranges from about 2% to about 15%.

14. Use according to claim 13, wherein said insulin is human recombinant insulin.

Said solid insulin dose releases insulin into said patient's blood stream and has an absolute bioavailability of insulin of at least about 60% and/or an absolute bioavailability of insulin of about 72-129% compared to subcutaneously injected doses of insulin. 14. Use according to claim 13, which provides a range of relative bioavailability.