JPWO2021048817A5 - - Google Patents
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- JPWO2021048817A5 JPWO2021048817A5 JP2022516406A JP2022516406A JPWO2021048817A5 JP WO2021048817 A5 JPWO2021048817 A5 JP WO2021048817A5 JP 2022516406 A JP2022516406 A JP 2022516406A JP 2022516406 A JP2022516406 A JP 2022516406A JP WO2021048817 A5 JPWO2021048817 A5 JP WO2021048817A5
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- pharmaceutical formulation
- risperidone
- formulation
- formulation according
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- 238000000034 method Methods 0.000 claims description 34
- 239000000203 mixture Substances 0.000 claims description 34
- 239000008194 pharmaceutical composition Substances 0.000 claims description 33
- 238000009472 formulation Methods 0.000 claims description 32
- -1 poly(lactic acid) Polymers 0.000 claims description 32
- RAPZEAPATHNIPO-UHFFFAOYSA-N risperidone Chemical compound FC1=CC=C2C(C3CCN(CC3)CCC=3C(=O)N4CCCCC4=NC=3C)=NOC2=C1 RAPZEAPATHNIPO-UHFFFAOYSA-N 0.000 claims description 26
- 229960001534 risperidone Drugs 0.000 claims description 26
- 208000020016 psychiatric disease Diseases 0.000 claims description 24
- 229920000359 diblock copolymer Polymers 0.000 claims description 16
- 229920000428 triblock copolymer Polymers 0.000 claims description 16
- 229920000747 poly(lactic acid) Polymers 0.000 claims description 12
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 6
- 229940071643 prefilled syringe Drugs 0.000 claims description 6
- 150000003839 salts Chemical class 0.000 claims description 6
- 229920001427 mPEG Polymers 0.000 claims description 4
- 239000003960 organic solvent Substances 0.000 claims description 4
- 239000000825 pharmaceutical preparation Substances 0.000 claims description 4
- 229920001223 polyethylene glycol Polymers 0.000 claims description 4
- 238000007920 subcutaneous administration Methods 0.000 claims description 4
- URAYPUMNDPQOKB-UHFFFAOYSA-N triacetin Chemical compound CC(=O)OCC(OC(C)=O)COC(C)=O URAYPUMNDPQOKB-UHFFFAOYSA-N 0.000 claims description 4
- 208000020925 Bipolar disease Diseases 0.000 claims description 2
- 210000001015 abdomen Anatomy 0.000 claims description 2
- 230000001186 cumulative effect Effects 0.000 claims description 2
- 235000013773 glyceryl triacetate Nutrition 0.000 claims description 2
- 239000001087 glyceryl triacetate Substances 0.000 claims description 2
- 238000000338 in vitro Methods 0.000 claims description 2
- 201000000980 schizophrenia Diseases 0.000 claims description 2
- 229960002622 triacetin Drugs 0.000 claims description 2
- YZWRNSARCRTXDS-UHFFFAOYSA-N tripropionin Chemical compound CCC(=O)OCC(OC(=O)CC)COC(=O)CC YZWRNSARCRTXDS-UHFFFAOYSA-N 0.000 claims description 2
- 238000012986 modification Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 230000000153 supplemental effect Effects 0.000 description 1
Description
本明細書に開示される特許、特許出願、及び刊行物は全て、各々の個々の刊行物が引用により具体的かつ個別的に組み込まれることが示される場合と同じ程度に引用により本明細書中に組み込まれる。本発明は、好ましい実施態様及び任意選択の特徴によって具体的に開示されているが、本明細書に開示される概念の修正及び変形が当業者によって使用され得ること、並びにそのような修正及び変形が添付の特許請求の範囲によって定義される本発明の範囲内に含まれると考えられることが理解されるべきである。
本件出願は、以下の態様の発明を提供する。
（態様１）
対象の精神医学的疾患又は障害を治療する方法であって、該対象に、21日毎に1回以下の頻度で、
a)リスペリドン換算で約250～400mg/mLの濃度のリスペリドン又はその医薬として許容し得る塩;
b)式:
ポリ(乳酸)v-ポリ(エチレングリコール)w, -ポリ(乳酸)x
(式中、v及びxは、24～682の範囲の反復単位の数であり、かつwは、4～273の範囲の反復単位の数であり、かつv=x又はv≠xである)
を有する生分解性トリブロックコポリマー;
c)式:
メトキシポリ(エチレングリコール)y-ポリ(乳酸)z
(式中、y及びzは反復単位の数であり、ここで、yは、3～45の範囲の反復単位の数であり、かつzは、7～327の範囲の反復単位の数である)
を有する生分解性ジブロックコポリマー;
:を含み、かつ
ここで、(b)の生分解性トリブロックコポリマーと(c)の生分解性ジブロックコポリマーの比が、水性環境中で不溶性である該製剤中、1:3～1:8又は1:1～1:19又は3:2～1:19である、1mL以下の医薬製剤
:を皮下投与することを含む、前記方法。
（態様２）
前記リスペリドンがリスペリドン塩基である、態様1記載の方法。
（態様３）
前記リスペリドン又は前記その医薬として許容し得る塩の濃度がリスペリドン換算で300mg/mL～400mg/mLである、態様1又は2記載の方法。
（態様４）
前記トリブロックコポリマーが前記製剤の総重量の約3％～20％(w/w％)の量で存在する、態様1～3のいずれか一項記載の方法。
（態様５）
前記トリブロックコポリマーが前記製剤の総重量の約5％～15％(w/w％)の量で存在する、態様4記載の方法。
（態様６）
前記ジブロックコポリマーが前記製剤の総重量の約8％～25％(w/w％)の量で存在する、態様1～5のいずれか一項記載の方法。
（態様７）
前記ジブロックコポリマーが前記製剤の総重量の約10％～20％(w/w％)の量で存在する、態様6記載の方法。
（態様８）
前記トリブロック及びジブロックコポリマーが前記製剤の総重量の約20％～約50％(w/w％)の総量で存在する、態様1～7のいずれか一項記載の方法。
（態様９）
前記トリブロック及びジブロックコポリマーが前記製剤の総重量の約20％～30％(w/w％)の総量で存在する、態様8記載の方法。
（態様１０）
前記製剤がDMSOである水溶性有機溶媒をさらに含む、態様1～9のいずれか一項記載の方法。
（態様１１）
前記製剤が、トリアセチン、トリプロピオニン、又はこれらの混合物をさらに含む、態様10記載の方法。
（態様１２）
前記有機溶媒が前記製剤の総重量の約35％～約55％(w/w％)の量で存在する、態様10又は11記載の方法。
（態様１３）
前記投与が対象の精神医学的疾患又は障害を21日～90日間治療するのに有効である、態様1～12のいずれか一項記載の方法。
（態様１４）
前記投与が対象の精神医学的疾患又は障害を28日～90日間治療するのに有効である、態様1～12のいずれか一項記載の方法。
（態様１５）
前記投与が対象の精神医学的疾患又は障害を28日～56日間治療するのに有効である、態様1～12のいずれか一項記載の方法。
（態様１６）
前記製剤中のリスペリドンの約15w％未満が投与後24時間で累積的に放出される、態様1～15のいずれか一項記載の方法。
（態様１７）
前記製剤中のリスペリドンの約7w％～約15w％が投与後24時間で累積的に放出される、態様16記載の方法。
（態様１８）
前記製剤中のリスペリドンの約50w％～約80w％が投与後30日で累積的に放出される、態様13～17のいずれか一項記載の方法。
（態様１９）
前記製剤中のリスペリドンの約70w％～約98％w％が投与後60日で累積的に放出される、態様13～18のいずれか一項記載の方法。
（態様２０）
前記累積放出が本明細書に開示されるインビトロ放出(IVR)法によって決定される、態様13～19のいずれか一項記載の方法。
（態様２１）
前記精神医学的疾患又は障害が統合失調症又は双極性障害である、態様1～20のいずれか一項記載の方法。
（態様２２）
前記方法がローディング用量の又は補助的な経口リスペリドンの非存在下で実施される、態様1～21のいずれか一項記載の方法。
（態様２３）
少なくとも6カ月間にわたる実施のための、態様1～22のいずれか一項記載の方法。
（態様２４）
少なくとも15カ月間にわたる実施のための、態様23記載の方法。
（態様２５）
前記製剤が単一の予充填シリンジ(PFS)中に提示される、態様1～24のいずれか一項記載の方法。
（態様２６）
前記予充填シリンジ中の容量が0.1mL～0.8mLである、態様25記載の方法。
（態様２７）
腹部への皮下投与のための、態様1～26のいずれか一項記載の方法。
（態様２８）
上腕への皮下投与のための、態様1～27のいずれか一項記載の方法。
（態様２９）
前記製剤が前記対象への投与後に切除可能である、態様1～28のいずれか一項記載の方法。
（態様３０）
精神医学的疾患又は障害を治療するための医薬製剤であって、1mL以下の:
a)リスペリドン換算で約250～400mg/mLの濃度のリスペリドン又はその医薬として許容し得る塩;
b)式:
ポリ(乳酸)v-ポリ(エチレングリコール)w, -ポリ(乳酸)x
(式中、v及びxは、24～682の範囲の反復単位の数であり、かつwは、4～273の範囲の反復単位の数であり、かつv=x又はv≠xである)
を有する生分解性トリブロックコポリマー;
c)式:
メトキシポリ(エチレングリコール)y-ポリ(乳酸)z
(式中、y及びzは反復単位の数であり、ここで、yは、3～45の範囲の反復単位の数であり、かつzは、7～327の範囲の反復単位の数である)
を有する生分解性ジブロックコポリマー;
を含み、かつ
ここで、(b)の生分解性トリブロックコポリマーと(c)の生分解性ジブロックコポリマーの比が、水性環境中で不溶性である該製剤中、1:3～1:8又は1:1～1:19又は3:2～1:19である、前記医薬製剤。
All patents, patent applications, and publications disclosed herein are herein incorporated by reference to the same extent as if each individual publication was specifically and individually indicated to be incorporated by reference. be incorporated into. Although the present invention has been specifically disclosed in terms of preferred embodiments and optional features, it is understood that modifications and variations of the concepts disclosed herein may be used by those skilled in the art, and that such modifications and variations may be used by those skilled in the art. It is to be understood that the following are considered to be within the scope of the invention as defined by the appended claims.
The present application provides the following aspects of the invention.
(Aspect 1)
A method of treating a psychiatric disease or disorder in a subject, the method comprising: administering to the subject no more than once every 21 days;
a) risperidone or a pharmaceutically acceptable salt thereof at a concentration of about 250 to 400 mg/mL in terms of risperidone;
b) Formula:
Poly(lactic acid) v-poly(ethylene glycol)w, -poly(lactic acid)x
(where v and x are the number of repeating units ranging from 24 to 682, and w is the number of repeating units ranging from 4 to 273, and v=x or v≠x)
a biodegradable triblock copolymer having;
c) Formula:
Methoxypoly(ethylene glycol)y-poly(lactic acid)z
(where y and z are the number of repeating units, where y is the number of repeating units ranging from 3 to 45, and z is the number of repeating units ranging from 7 to 327 )
a biodegradable diblock copolymer with;
contains : and
wherein the ratio of the biodegradable triblock copolymer of (b) to the biodegradable diblock copolymer of (c) is 1:3 to 1:8 or 1:1 in the formulation that is insoluble in an aqueous environment. ~1:19 or 3:2 to 1:19 of a pharmaceutical formulation of 1 mL or less
The method described above, comprising subcutaneously administering:
(Aspect 2)
The method according to embodiment 1, wherein the risperidone is risperidone base.
(Aspect 3)
The method according to aspect 1 or 2, wherein the concentration of the risperidone or the pharmaceutically acceptable salt thereof is 300 mg/mL to 400 mg/mL in terms of risperidone.
(Aspect 4)
4. The method of any one of embodiments 1-3, wherein the triblock copolymer is present in an amount of about 3% to 20% (w/w%) of the total weight of the formulation.
(Aspect 5)
5. The method of embodiment 4, wherein the triblock copolymer is present in an amount of about 5% to 15% (w/w%) of the total weight of the formulation.
(Aspect 6)
6. The method of any one of embodiments 1-5, wherein the diblock copolymer is present in an amount of about 8% to 25% (w/w%) of the total weight of the formulation.
(Aspect 7)
7. The method of embodiment 6, wherein the diblock copolymer is present in an amount of about 10% to 20% (w/w%) of the total weight of the formulation.
(Aspect 8)
8. The method of any one of embodiments 1-7, wherein the triblock and diblock copolymers are present in a total amount of about 20% to about 50% (w/w%) of the total weight of the formulation.
(Aspect 9)
9. The method of embodiment 8, wherein the triblock and diblock copolymers are present in a total amount of about 20% to 30% (w/w%) of the total weight of the formulation.
(Aspect 10)
10. The method according to any one of embodiments 1 to 9, wherein the formulation further comprises a water-soluble organic solvent which is DMSO.
(Aspect 11)
11. The method of embodiment 10, wherein the formulation further comprises triacetin, tripropionine, or a mixture thereof.
(Aspect 12)
12. The method of embodiment 10 or 11, wherein the organic solvent is present in an amount of about 35% to about 55% (w/w%) of the total weight of the formulation.
(Aspect 13)
13. The method of any one of embodiments 1-12, wherein said administration is effective to treat a psychiatric disease or disorder in a subject for 21 to 90 days.
(Aspect 14)
13. The method of any one of embodiments 1-12, wherein said administration is effective to treat a psychiatric disease or disorder in a subject for 28 to 90 days.
(Aspect 15)
13. The method of any one of embodiments 1-12, wherein said administration is effective to treat a psychiatric disease or disorder in a subject for 28 to 56 days.
(Aspect 16)
16. The method of any one of embodiments 1-15, wherein less than about 15 w% of the risperidone in the formulation is cumulatively released 24 hours after administration.
(Aspect 17)
17. The method of embodiment 16, wherein about 7w% to about 15w% of the risperidone in the formulation is cumulatively released 24 hours after administration.
(Aspect 18)
18. The method of any one of embodiments 13-17, wherein about 50w% to about 80w% of the risperidone in the formulation is cumulatively released 30 days after administration.
(Aspect 19)
19. The method of any one of embodiments 13-18, wherein from about 70 w% to about 98% w% of the risperidone in the formulation is cumulatively released 60 days after administration.
(Aspect 20)
20. The method according to any one of embodiments 13 to 19, wherein said cumulative release is determined by an in vitro release (IVR) method as disclosed herein.
(Aspect 21)
21. The method according to any one of embodiments 1 to 20, wherein the psychiatric disease or disorder is schizophrenia or bipolar disorder.
(Aspect 22)
22. The method according to any one of embodiments 1 to 21, wherein the method is carried out in the absence of a loading dose or supplemental oral risperidone.
(Aspect 23)
23. The method according to any one of embodiments 1 to 22, for implementation over a period of at least 6 months.
(Aspect 24)
24. The method according to embodiment 23, for implementation over a period of at least 15 months.
(Aspect 25)
25. The method according to any one of embodiments 1 to 24, wherein the formulation is presented in a single prefilled syringe (PFS).
(Aspect 26)
26. The method of embodiment 25, wherein the volume in the prefilled syringe is between 0.1 mL and 0.8 mL.
(Aspect 27)
27. The method according to any one of embodiments 1 to 26, for subcutaneous administration to the abdomen.
(Aspect 28)
28. A method according to any one of embodiments 1 to 27 for subcutaneous administration to the upper arm.
(Aspect 29)
29. The method of any one of embodiments 1-28, wherein said formulation is resectable after administration to said subject.
(Aspect 30)
Pharmaceutical preparations for the treatment of psychiatric diseases or disorders, with a volume of 1 mL or less:
a) risperidone or a pharmaceutically acceptable salt thereof at a concentration of about 250 to 400 mg/mL in terms of risperidone;
b) Formula:
Poly(lactic acid) v-poly(ethylene glycol)w, -poly(lactic acid)x
(where v and x are the number of repeating units ranging from 24 to 682, and w is the number of repeating units ranging from 4 to 273, and v=x or v≠x)
a biodegradable triblock copolymer having;
c) Formula:
Methoxypoly(ethylene glycol)y-poly(lactic acid)z
(where y and z are the number of repeating units, where y is the number of repeating units ranging from 3 to 45, and z is the number of repeating units ranging from 7 to 327 )
a biodegradable diblock copolymer with;
including, and
wherein the ratio of the biodegradable triblock copolymer of (b) to the biodegradable diblock copolymer of (c) is 1:3 to 1:8 or 1:1 in the formulation that is insoluble in an aqueous environment. ˜1:19 or 3:2 to 1:19.
Claims (30)
a)リスペリドン換算で約250～400mg/mLの濃度のリスペリドン又はその医薬として許容し得る塩;
b)式:ポリ(乳酸)v-ポリ(エチレングリコール)w, -ポリ(乳酸)x
(式中、v及びxは、24～682の範囲の反復単位の数であり、かつwは、4～273の範囲の反復単位の数であり、かつv=x又はv≠xである)を有する生分解性トリブロックコポリマー;及び
c)式:メトキシポリ(エチレングリコール)y-ポリ(乳酸)z
(式中、y及びzは反復単位の数であり、ここで、yは、3～45の範囲の反復単位の数であり、かつzは、7～327の範囲の反復単位の数である)を有する生分解性ジブロックコポリマー;を含み、
(b)の生分解性トリブロックコポリマーと(c)の生分解性ジブロックコポリマーの比が、水性環境中で不溶性である該医薬製剤中、1:3～1:8又は1:1～1:19又は3:2～1:19であり、
該医薬製剤は対象に1mL以下が投与され、かつ
該医薬製剤は、21日毎に1回以下の頻度で該対象に皮下投与される、前記医薬製剤。 A pharmaceutical preparation for treating a psychiatric disease or disorder, comprising:
a) risperidone or a pharmaceutically acceptable salt thereof at a concentration of about 250 to 400 mg/mL in terms of risperidone;
b) Formula: poly(lactic acid) v-poly(ethylene glycol) w, -poly(lactic acid) x
(where v and x are the number of repeating units ranging from 24 to 682, and w is the number of repeating units ranging from 4 to 273, and v=x or v≠x) a biodegradable triblock copolymer having; and
c) Formula: Methoxypoly(ethylene glycol)y-poly(lactic acid)z
(where y and z are the number of repeating units, where y is the number of repeating units ranging from 3 to 45, and z is the number of repeating units ranging from 7 to 327 ) having a biodegradable diblock copolymer;
In said pharmaceutical formulation which is insoluble in an aqueous environment, the ratio of the biodegradable triblock copolymer of (b) to the biodegradable diblock copolymer of (c) is from 1:3 to 1:8 or from 1:1 to 1. :19 or 3:2 to 1:19,
1 mL or less of the pharmaceutical formulation is administered to the subject; and the pharmaceutical formulation is administered subcutaneously to the subject no more frequently than once every 21 days.
a)リスペリドン換算で約250～400mg/mLの濃度のリスペリドン又はその医薬として許容し得る塩;
b)式:ポリ(乳酸)v-ポリ(エチレングリコール)w, -ポリ(乳酸)x
(式中、v及びxは、24～682の範囲の反復単位の数であり、かつwは、4～273の範囲の反復単位の数であり、かつv=x又はv≠xである)を有する生分解性トリブロックコポリマー;及び
c)式:メトキシポリ(エチレングリコール)y-ポリ(乳酸)z
(式中、y及びzは反復単位の数であり、ここで、yは、3～45の範囲の反復単位の数であり、かつzは、7～327の範囲の反復単位の数である)を有する生分解性ジブロックコポリマー;
を含み、かつ
ここで、(b)の生分解性トリブロックコポリマーと(c)の生分解性ジブロックコポリマーの比が、水性環境中で不溶性である該製剤中1:3～1:8又は1:1～1:19又は3:2～1:19である、前記医薬製剤。 A pharmaceutical preparation for treating a psychiatric disease or disorder, comprising:
a) risperidone or a pharmaceutically acceptable salt thereof at a concentration of about 250 to 400 mg/mL in terms of risperidone;
b) Formula: poly(lactic acid) v-poly(ethylene glycol) w, -poly(lactic acid) x
(where v and x are the number of repeating units ranging from 24 to 682, and w is the number of repeating units ranging from 4 to 273, and v=x or v≠x) a biodegradable triblock copolymer having; and
c) Formula: Methoxypoly(ethylene glycol)y-poly(lactic acid)z
(where y and z are the number of repeating units, where y is the number of repeating units ranging from 3 to 45, and z is the number of repeating units ranging from 7 to 327 ) with biodegradable diblock copolymers;
and wherein the ratio of the biodegradable triblock copolymer of (b) to the biodegradable diblock copolymer of (c) is 1:3 to 1:8 or The above pharmaceutical formulation, wherein the ratio is 1:1 to 1:19 or 3:2 to 1:19.
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201962900061P | 2019-09-13 | 2019-09-13 | |
| US62/900,061 | 2019-09-13 | ||
| PCT/IB2020/058474 WO2021048817A1 (en) | 2019-09-13 | 2020-09-11 | Drug delivery formulations |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2022548616A JP2022548616A (en) | 2022-11-21 |
| JPWO2021048817A5 true JPWO2021048817A5 (en) | 2024-01-05 |
Family
ID=72521677
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2022516406A Pending JP2022548616A (en) | 2019-09-13 | 2020-09-11 | drug delivery formulation |
Country Status (11)
| Country | Link |
|---|---|
| US (2) | US20220331240A1 (en) |
| EP (1) | EP4027973A1 (en) |
| JP (1) | JP2022548616A (en) |
| KR (1) | KR20220062372A (en) |
| CN (1) | CN114727946A (en) |
| AU (1) | AU2020346455A1 (en) |
| BR (1) | BR112022004535A2 (en) |
| CA (1) | CA3153793A1 (en) |
| IL (1) | IL291283A (en) |
| MX (1) | MX2022003051A (en) |
| WO (1) | WO2021048817A1 (en) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2024511353A (en) * | 2021-03-17 | 2024-03-13 | メドインセルル エス．エー． | Long-acting injectable formulation containing risperidone and biodegradable polymers |
Family Cites Families (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP1024790A4 (en) * | 1997-08-08 | 2000-10-25 | Univ Utah Res Found | Injectable biodegradable block copolymer gels for use in drug delivery |
| CN101584652B (en) * | 2009-06-19 | 2012-06-20 | 上海医药集团股份有限公司 | Risperidone sustained-release gel injection and preparation method thereof |
| SG191414A1 (en) * | 2010-12-29 | 2013-08-30 | Medincell | Biodegradable drug delivery compositions |
| EP3219310A3 (en) * | 2011-10-24 | 2017-11-29 | Braeburn Pharmaceuticals, Inc. | Implantable drug delivery compositions and methods of treatment thereof |
| CN104582733B (en) * | 2012-06-27 | 2017-07-04 | 美蒂森 | For the biodegradable drug delivery system of hydrophobic composition |
| BR112015022023B1 (en) * | 2013-03-11 | 2022-12-06 | Durect Corporation | INJECTABLE CONTROLLED RELEASE COMPOSITION COMPRISING HIGH VISCOSITY LIQUID CARRIER |
| US11612563B2 (en) * | 2017-07-17 | 2023-03-28 | Medincell | Pharmaceutical composition |
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2020
- 2020-09-11 EP EP20772437.8A patent/EP4027973A1/en active Pending
- 2020-09-11 BR BR112022004535A patent/BR112022004535A2/en unknown
- 2020-09-11 MX MX2022003051A patent/MX2022003051A/en unknown
- 2020-09-11 JP JP2022516406A patent/JP2022548616A/en active Pending
- 2020-09-11 KR KR1020227012200A patent/KR20220062372A/en unknown
- 2020-09-11 CN CN202080077874.0A patent/CN114727946A/en active Pending
- 2020-09-11 WO PCT/IB2020/058474 patent/WO2021048817A1/en unknown
- 2020-09-11 AU AU2020346455A patent/AU2020346455A1/en active Pending
- 2020-09-11 US US17/642,410 patent/US20220331240A1/en active Pending
- 2020-09-11 CA CA3153793A patent/CA3153793A1/en active Pending
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2022
- 2022-03-10 IL IL291283A patent/IL291283A/en unknown
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2023
- 2023-12-20 US US18/391,243 patent/US20240156722A1/en active Pending
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