MiRNA (micro ribonucleic acid) interferent capable of potentially regulating and controlling leukemia and application thereof

文档序号:109486 发布日期:2021-10-19 浏览:42次 中文

阅读说明:本技术 一种潜在可调控白血病的miRNA干扰物及其应用 (MiRNA (micro ribonucleic acid) interferent capable of potentially regulating and controlling leukemia and application thereof ) 是由 不公告发明人 于 2021-08-06 设计创作,主要内容包括:本发明公开了一种潜在可调控白血病的miRNA干扰物及其应用,属于医学制造技术领域。所属的潜在可调控白血病的miRNA干扰物,以重量份计,包括以下组分:聚乙烯醇为30份-50份,海藻酸钠为5份-10份,酮洛芬为0.8份-1.5份,聚肌苷酸为0.5份-1.1份。所述的潜在可调控白血病的miRNA干扰物的应用,所述的miRNA干扰物的剂型为药学上可接受的剂型,具体使用时选择口服剂形式。本发明创新设置新的干扰物,此干扰物可与miRNA进行配合使用,提高miRNA的使用效果。与传统技术相比,充分利用海藻酸钠与酮洛芬的有效结合,提高聚肌苷酸与miRNA的结合力度,降低在人体内的降解程度。(The invention discloses a potential adjustable leukemia miRNA (micro ribonucleic acid) interferent and application thereof, belonging to the technical field of medical manufacturing. The miRNA interferent for potential regulation and control of leukemia comprises the following components in parts by weight: 30 to 50 portions of polyvinyl alcohol, 5 to 10 portions of sodium alginate, 0.8 to 1.5 portions of ketoprofen and 0.5 to 1.1 portions of polyinosinic acid. The miRNA interferent is applied, the dosage form of the miRNA interferent is pharmaceutically acceptable, and the dosage form is selected when the miRNA interferent is used specifically. The invention innovatively arranges a new interference substance which can be matched with miRNA for use, thereby improving the using effect of miRNA. Compared with the prior art, the effective combination of sodium alginate and ketoprofen is fully utilized, the combination strength of polyinosinic acid and miRNA is improved, and the degradation degree in a human body is reduced.)

1. A potentially leukemia-regulatable miRNA interferon, comprising:

the coating comprises the following components in parts by weight:

30 to 50 portions of polyvinyl alcohol,

5 to 10 portions of sodium alginate, namely,

0.8 to 1.5 portions of ketoprofen,

0.5 to 1.1 portions of polyinosinic acid.

2. The potentially leukemia-regulatable miRNA interferent of claim 1, wherein:

the coating comprises the following components in parts by weight:

35 to 45 portions of polyvinyl alcohol,

5 to 10 portions of sodium alginate, namely,

0.8 to 1.5 portions of ketoprofen,

0.5 to 1.1 portions of polyinosinic acid.

3. The potentially leukemia-regulatable miRNA interferent of claim 2, wherein:

the coating comprises the following components in parts by weight:

40 parts of polyvinyl alcohol, namely 40 parts of polyvinyl alcohol,

8 parts of sodium alginate, namely 8 parts of sodium alginate,

1 part of ketoprofen,

0.8 part of polyinosinic acid.

4. The potentially leukemia-regulatable miRNA interferent of claim 1, wherein:

the purity of the polyvinyl alcohol is 99%.

5. The potentially leukemia-regulatable miRNA interferent of claim 1, wherein:

the purity of the sodium alginate is analytically pure.

6. The potentially leukemia-regulatable miRNA interferent of claim 1, wherein:

the purity of the ketoprofen is chromatographic purity.

7. The potentially leukemia-regulatable miRNA interferent of claim 1, wherein:

the purity of the polyinosinic acid is analytical purity.

8. The potentially leukemia-regulatable miRNA interferent of claim 1, wherein:

the sodium alginate is in a powdery form;

the form of the ketoprofen is powdery;

the polyinosinic acid is in a powder form.

9. The application of miRNA interferent capable of potentially regulating leukemia is characterized in that:

the dosage form of the miRNA interferent is a pharmaceutically acceptable dosage form.

10. The use of miRNA interferents with potential regulable leukemia according to claim 9, wherein:

the dosage form of the miRNA interferent is oral agent.

Technical Field

The invention belongs to the technical field of medical manufacturing, and particularly relates to a potential leukemia regulable miRNA (micro ribonucleic acid) interferent and application thereof.

Background

Acute leukemia is a clonal malignant disease derived from hematopoietic stem cells, and the abnormal proliferation of leukemia cells in bone marrow leads to the inhibition of normal hematopoiesis, and clinically shows anemia, hemorrhage, infection and the like. Acute Myeloid Leukemia (AML) is the most common adult acute leukemia, the incidence rate of AML is gradually increased in recent years, and although the complete remission rate of geisha patients can reach 50-70% by the existing treatment method, the fatality rate of the disease is still high, and the individual layered treatment aiming at different patients becomes a concern of people. The comprehensive research on the effect of the gene on the AML occurrence and development and the prognostic influence is helpful for searching effective anti-leukemia angiogenesis treatment targets, thereby further guiding clinical individualized treatment. microRNAs (miRNAs) are rich non-protein coding small molecular RNAs, and the miRNAs are mainly combined with a 3' -UTR region of target mRNA, can inhibit translation of the mRNA or directly degrade the mRNA, and regulate various biological functions. It is estimated that about 1/3 genes in organisms are regulated by mirnas. Detecting the expression level of miRNA can provide reference for clinical diagnosis of cancer. The abnormal expression of miRNA directly causes the abnormal expression of some genes related to disease occurrence, and induces the occurrence of cancer. It has been reported that miRNA plays an important role in acute myeloid leukemia by regulating the expression of target gene mRNA. In future clinical treatment, the miRNA not only can be a novel marker related to early diagnosis and disease process of acute myelogenous leukemia, but also is expected to treat diseases such as acute myelogenous leukemia and the like by changing the expression of the miRNA or the expression of a target gene of the miRNA.

However, direct use of miRNA is easily degraded by in vivo enzymes, and therefore there is an urgent need for an interferent that can stabilize miRNA.

Disclosure of Invention

Problems to be solved

Aiming at the problems in the prior art, the invention provides the miRNA interferent capable of potentially regulating and controlling leukemia and the application thereof, the process is simple, and particularly, the prepared miRNA interferent can be effectively combined with miRNA.

Technical scheme

In order to solve the above problems, the present invention adopts the following technical solutions.

A potential leukemia-controllable miRNA (micro ribonucleic acid) interferent comprises the following components in parts by weight:

30 to 50 portions of polyvinyl alcohol,

5 to 10 portions of sodium alginate, namely,

0.8 to 1.5 portions of ketoprofen,

0.5 to 1.1 portions of polyinosinic acid.

Among the above mentioned miRNA interferents for potential regulation of leukemia,

the coating comprises the following components in parts by weight:

35 to 45 portions of polyvinyl alcohol,

5 to 10 portions of sodium alginate, namely,

0.8 to 1.5 portions of ketoprofen,

0.5 to 1.1 portions of polyinosinic acid.

Among the above mentioned miRNA interferents for potential regulation of leukemia,

the coating comprises the following components in parts by weight:

40 parts of polyvinyl alcohol, namely 40 parts of polyvinyl alcohol,

8 parts of sodium alginate, namely 8 parts of sodium alginate,

1 part of ketoprofen,

0.8 part of polyinosinic acid.

Among the above mentioned miRNA interferents for potential regulation of leukemia,

the purity of the polyvinyl alcohol is 99%.

Among the above mentioned miRNA interferents for potential regulation of leukemia,

the purity of the sodium alginate is analytically pure.

Among the above mentioned miRNA interferents for potential regulation of leukemia,

the purity of the ketoprofen is chromatographic purity.

Among the above mentioned miRNA interferents for potential regulation of leukemia,

the purity of the polyinosinic acid is analytical purity.

Among the above mentioned miRNA interferents for potential regulation of leukemia,

the sodium alginate is in a powdery form;

the form of the ketoprofen is powdery;

the polyinosinic acid is in a powder form.

The application of a miRNA (micro ribonucleic acid) interferent capable of potentially regulating leukemia is disclosed, and the dosage form of the miRNA interferent is a pharmaceutically acceptable dosage form.

In the application of the miRNA interferent for potentially regulating leukemia, the dosage form of the miRNA interferent is oral preparation.

Has the beneficial effects of

Compared with the prior art, the invention has the beneficial effects that:

the invention innovatively arranges a new interference substance which can be matched with miRNA for use, thereby improving the using effect of miRNA. Compared with the prior art, the effective combination of sodium alginate and ketoprofen is fully utilized, the combination strength of polyinosinic acid and miRNA is improved, and the degradation degree in a human body is reduced.

Detailed Description

The invention is further described with reference to specific examples.

Example 1

The miRNA interferent for potentially regulating leukemia comprises the following components in parts by weight:

30 parts of polyvinyl alcohol, namely 30 parts of polyvinyl alcohol,

10 parts of sodium alginate, namely 10 parts of sodium alginate,

0.8 part of ketoprofen,

1.1 parts of polyinosinic acid.

Among the above mentioned miRNA interferents for potential regulation of leukemia,

the purity of the polyvinyl alcohol is 99%.

Among the above mentioned miRNA interferents for potential regulation of leukemia,

the purity of the sodium alginate is analytically pure.

Among the above mentioned miRNA interferents for potential regulation of leukemia,

the purity of the ketoprofen is chromatographic purity.

Among the above mentioned miRNA interferents for potential regulation of leukemia,

the purity of the polyinosinic acid is analytical purity.

Among the above mentioned miRNA interferents for potential regulation of leukemia,

the sodium alginate is in a powdery form;

the form of the ketoprofen is powdery;

the polyinosinic acid is in a powder form.

The miRNA interferent is used for potentially regulating and controlling leukemia, and the dosage form of the miRNA interferent is pharmaceutically acceptable.

In the application of the miRNA interferent for potentially regulating leukemia, the dosage form of the miRNA interferent is oral preparation.

Example 2

The miRNA interferent for potentially regulating leukemia comprises the following components in parts by weight:

50 parts of polyvinyl alcohol, namely polyvinyl alcohol,

5 parts of sodium alginate, namely sodium alginate,

1.5 parts of ketoprofen,

0.5 part of polyinosinic acid.

Among the above mentioned miRNA interferents for potential regulation of leukemia,

the purity of the polyvinyl alcohol is 99%.

Among the above mentioned miRNA interferents for potential regulation of leukemia,

the purity of the sodium alginate is analytically pure.

Among the above mentioned miRNA interferents for potential regulation of leukemia,

the purity of the ketoprofen is chromatographic purity.

Among the above mentioned miRNA interferents for potential regulation of leukemia,

the purity of the polyinosinic acid is analytical purity.

Among the above mentioned miRNA interferents for potential regulation of leukemia,

the sodium alginate is in a powdery form;

the form of the ketoprofen is powdery;

the polyinosinic acid is in a powder form.

The miRNA interferent is used for potentially regulating and controlling leukemia, and the dosage form of the miRNA interferent is pharmaceutically acceptable.

In the application of the miRNA interferent for potentially regulating leukemia, the dosage form of the miRNA interferent is oral preparation.

Example 3

The miRNA interferent for potentially regulating leukemia comprises the following components in parts by weight:

35 parts of polyvinyl alcohol, namely polyvinyl alcohol,

10 parts of sodium alginate, namely 10 parts of sodium alginate,

0.8 part of ketoprofen,

1.1 parts of polyinosinic acid.

Among the above mentioned miRNA interferents for potential regulation of leukemia,

the purity of the polyvinyl alcohol is 99%.

Among the above mentioned miRNA interferents for potential regulation of leukemia,

the purity of the sodium alginate is analytically pure.

Among the above mentioned miRNA interferents for potential regulation of leukemia,

the purity of the ketoprofen is chromatographic purity.

Among the above mentioned miRNA interferents for potential regulation of leukemia,

the purity of the polyinosinic acid is analytical purity.

Among the above mentioned miRNA interferents for potential regulation of leukemia,

the sodium alginate is in a powdery form;

the form of the ketoprofen is powdery;

the polyinosinic acid is in a powder form.

The miRNA interferent is used for potentially regulating and controlling leukemia, and the dosage form of the miRNA interferent is pharmaceutically acceptable.

In the application of the miRNA interferent for potentially regulating leukemia, the dosage form of the miRNA interferent is oral preparation.

Example 4

The miRNA interferent for potentially regulating leukemia comprises the following components in parts by weight:

45 parts of polyvinyl alcohol, namely 45 parts of polyvinyl alcohol,

5 parts of sodium alginate, namely sodium alginate,

1.5 parts of ketoprofen,

0.5 part of polyinosinic acid.

Among the above mentioned miRNA interferents for potential regulation of leukemia,

the purity of the polyvinyl alcohol is 99%.

Among the above mentioned miRNA interferents for potential regulation of leukemia,

the purity of the sodium alginate is analytically pure.

Among the above mentioned miRNA interferents for potential regulation of leukemia,

the purity of the ketoprofen is chromatographic purity.

Among the above mentioned miRNA interferents for potential regulation of leukemia,

the purity of the polyinosinic acid is analytical purity.

Among the above mentioned miRNA interferents for potential regulation of leukemia,

the sodium alginate is in a powdery form;

the form of the ketoprofen is powdery;

the polyinosinic acid is in a powder form.

The miRNA interferent is used for potentially regulating and controlling leukemia, and the dosage form of the miRNA interferent is pharmaceutically acceptable.

In the application of the miRNA interferent for potentially regulating leukemia, the dosage form of the miRNA interferent is oral preparation.

Example 5

The miRNA interferent for potentially regulating leukemia comprises the following components in parts by weight:

40 parts of polyvinyl alcohol, namely 40 parts of polyvinyl alcohol,

8 parts of sodium alginate, namely 8 parts of sodium alginate,

1 part of ketoprofen,

0.8 part of polyinosinic acid.

Among the above mentioned miRNA interferents for potential regulation of leukemia,

the purity of the polyvinyl alcohol is 99%.

Among the above mentioned miRNA interferents for potential regulation of leukemia,

the purity of the sodium alginate is analytically pure.

Among the above mentioned miRNA interferents for potential regulation of leukemia,

the purity of the ketoprofen is chromatographic purity.

Among the above mentioned miRNA interferents for potential regulation of leukemia,

the purity of the polyinosinic acid is analytical purity.

Among the above mentioned miRNA interferents for potential regulation of leukemia,

the sodium alginate is in a powdery form;

the form of the ketoprofen is powdery;

the polyinosinic acid is in a powder form.

The miRNA interferent is used for potentially regulating and controlling leukemia, and the dosage form of the miRNA interferent is pharmaceutically acceptable.

In the application of the miRNA interferent for potentially regulating leukemia, the dosage form of the miRNA interferent is oral preparation.

Comparative example 1

The miRNA interferent for potentially regulating leukemia comprises the following components in parts by weight:

55 parts of polyvinyl alcohol, namely polyvinyl alcohol,

15 parts of sodium alginate, namely sodium alginate,

2 parts of ketoprofen,

and 1.8 parts of polyinosinic acid.

Among the above mentioned miRNA interferents for potential regulation of leukemia,

the purity of the polyvinyl alcohol is 99%.

Among the above mentioned miRNA interferents for potential regulation of leukemia,

the purity of the sodium alginate is analytically pure.

Among the above mentioned miRNA interferents for potential regulation of leukemia,

the purity of the ketoprofen is chromatographic purity.

Among the above mentioned miRNA interferents for potential regulation of leukemia,

the purity of the polyinosinic acid is analytical purity.

Among the above mentioned miRNA interferents for potential regulation of leukemia,

the sodium alginate is in a powdery form;

the form of the ketoprofen is powdery;

the polyinosinic acid is in a powder form.

The miRNA interferent is used for potentially regulating and controlling leukemia, and the dosage form of the miRNA interferent is pharmaceutically acceptable.

In the application of the miRNA interferent for potentially regulating leukemia, the dosage form of the miRNA interferent is oral preparation.

Comparative example 2

The miRNA interferent for potentially regulating leukemia comprises the following components in parts by weight:

20 parts of polyvinyl alcohol, namely 20 parts of polyvinyl alcohol,

3 parts of sodium alginate, namely 3 parts of sodium alginate,

0.5 part of ketoprofen,

0.8 part of polyinosinic acid.

Among the above mentioned miRNA interferents for potential regulation of leukemia,

the purity of the polyvinyl alcohol is 99%.

Among the above mentioned miRNA interferents for potential regulation of leukemia,

the purity of the sodium alginate is analytically pure.

Among the above mentioned miRNA interferents for potential regulation of leukemia,

the purity of the ketoprofen is chromatographic purity.

Among the above mentioned miRNA interferents for potential regulation of leukemia,

the purity of the polyinosinic acid is analytical purity.

Among the above mentioned miRNA interferents for potential regulation of leukemia,

the sodium alginate is in a powdery form;

the form of the ketoprofen is powdery;

the polyinosinic acid is in a powder form.

The miRNA interferent is used for potentially regulating and controlling leukemia, and the dosage form of the miRNA interferent is pharmaceutically acceptable.

In the application of the miRNA interferent for potentially regulating leukemia, the dosage form of the miRNA interferent is oral preparation.

Comparative example 3

The miRNA interferent for potentially regulating leukemia comprises the following components in parts by weight:

40 parts of polyvinyl alcohol, namely 40 parts of polyvinyl alcohol,

8 parts of sodium alginate, namely 8 parts of sodium alginate,

1 part of ketoprofen.

Among the above mentioned miRNA interferents for potential regulation of leukemia,

the purity of the polyvinyl alcohol is 99%.

Among the above mentioned miRNA interferents for potential regulation of leukemia,

the purity of the sodium alginate is analytically pure.

Among the above mentioned miRNA interferents for potential regulation of leukemia,

the purity of the ketoprofen is chromatographic purity.

Among the above mentioned miRNA interferents for potential regulation of leukemia,

the sodium alginate is in a powdery form;

the form of the ketoprofen is powdery;

the polyinosinic acid is in a powder form.

The miRNA interferent is used for potentially regulating and controlling leukemia, and the dosage form of the miRNA interferent is pharmaceutically acceptable.

In the application of the miRNA interferent for potentially regulating leukemia, the dosage form of the miRNA interferent is oral preparation.

Comparative example 4

The miRNA interferent for potentially regulating leukemia comprises the following components in parts by weight:

40 parts of polyvinyl alcohol, namely 40 parts of polyvinyl alcohol,

8 parts of sodium alginate, namely 8 parts of sodium alginate,

0.8 part of polyinosinic acid.

Among the above mentioned miRNA interferents for potential regulation of leukemia,

the purity of the polyvinyl alcohol is 99%.

Among the above mentioned miRNA interferents for potential regulation of leukemia,

the purity of the sodium alginate is analytically pure.

Among the above mentioned miRNA interferents for potential regulation of leukemia,

the purity of the polyinosinic acid is analytical purity.

Among the above mentioned miRNA interferents for potential regulation of leukemia,

the sodium alginate is in a powdery form;

the form of the ketoprofen is powdery;

the polyinosinic acid is in a powder form.

The miRNA interferent is used for potentially regulating and controlling leukemia, and the dosage form of the miRNA interferent is pharmaceutically acceptable.

In the application of the miRNA interferent for potentially regulating leukemia, the dosage form of the miRNA interferent is oral preparation.

Comparative example 5

The miRNA interferent for potentially regulating leukemia comprises the following components in parts by weight:

40 parts of polyvinyl alcohol, namely 40 parts of polyvinyl alcohol,

8 parts of sodium alginate.

Among the above mentioned miRNA interferents for potential regulation of leukemia,

the purity of the polyvinyl alcohol is 99%.

Among the above mentioned miRNA interferents for potential regulation of leukemia,

the purity of the sodium alginate is analytically pure.

Among the above mentioned miRNA interferents for potential regulation of leukemia,

the sodium alginate is in a powdery form;

the form of the ketoprofen is powdery;

the polyinosinic acid is in a powder form.

The miRNA interferent is used for potentially regulating and controlling leukemia, and the dosage form of the miRNA interferent is pharmaceutically acceptable.

In the application of the miRNA interferent for potentially regulating leukemia, the dosage form of the miRNA interferent is oral preparation.

Comparative example 6

The miRNA interferent for potentially regulating leukemia comprises the following components in parts by weight:

40 parts of polyvinyl alcohol, namely 40 parts of polyvinyl alcohol,

1 part of ketoprofen,

0.8 part of polyinosinic acid.

Among the above mentioned miRNA interferents for potential regulation of leukemia,

the purity of the polyvinyl alcohol is 99%.

Among the above mentioned miRNA interferents for potential regulation of leukemia,

the purity of the ketoprofen is chromatographic purity.

Among the above mentioned miRNA interferents for potential regulation of leukemia,

the purity of the polyinosinic acid is analytical purity.

Among the above mentioned miRNA interferents for potential regulation of leukemia,

the sodium alginate is in a powdery form;

the form of the ketoprofen is powdery;

the polyinosinic acid is in a powder form.

The miRNA interferent is used for potentially regulating and controlling leukemia, and the dosage form of the miRNA interferent is pharmaceutically acceptable.

In the application of the miRNA interferent for potentially regulating leukemia, the dosage form of the miRNA interferent is oral preparation.

Comparative example 7

The miRNA interferent for potentially regulating leukemia comprises the following components in parts by weight:

40 parts of polyethylene glycol, namely 40 parts of polyethylene glycol,

8 parts of sodium alginate, namely 8 parts of sodium alginate,

1 part of ketoprofen,

0.8 part of polyinosinic acid.

Among the above mentioned miRNA interferents for potential regulation of leukemia,

the purity of the polyethylene glycol is 99%.

Among the above mentioned miRNA interferents for potential regulation of leukemia,

the purity of the sodium alginate is analytically pure.

Among the above mentioned miRNA interferents for potential regulation of leukemia,

the purity of the ketoprofen is chromatographic purity.

Among the above mentioned miRNA interferents for potential regulation of leukemia,

the purity of the polyinosinic acid is analytical purity.

Among the above mentioned miRNA interferents for potential regulation of leukemia,

the sodium alginate is in a powdery form;

the form of the ketoprofen is powdery;

the polyinosinic acid is in a powder form.

The miRNA interferent is used for potentially regulating and controlling leukemia, and the dosage form of the miRNA interferent is pharmaceutically acceptable.

In the application of the miRNA interferent for potentially regulating leukemia, the dosage form of the miRNA interferent is oral preparation.

Example 6

The products prepared in examples 1-5 and the products prepared in comparative examples 1-7 were selected for the following binding tests:

taking the invention granted in China as an example, the application number is CN201510549860.5, which relates to the application of miRNA-1277 in the diagnosis and treatment of acute myeloid leukemia. We explored the degree of binding of its product (interferent) to miRNA by mixing it with miRNA-1277.

Wherein the binding degree of the interference prepared in example 1 and miRNA is 90.2%;

wherein the binding degree of the interference prepared in example 2 and miRNA is 90.8%;

wherein the binding degree of the interference prepared in example 3 and miRNA is 90.5%;

wherein the binding degree of the interference prepared in example 4 and miRNA is 91.1%;

wherein the binding degree of the interference prepared in example 5 and miRNA is 91.4%;

wherein the binding degree of the interferent prepared in comparative example 1 to miRNA is 87.5%;

wherein the binding degree of the interferent prepared in comparative example 2 to miRNA is 88.3%;

wherein the binding degree of the interferent prepared in comparative example 3 to miRNA is 82.8%;

wherein the binding degree of the interferent prepared in comparative example 4 to miRNA is 80.1%;

wherein the binding degree of the interferent prepared in comparative example 5 to miRNA is 74.2%;

wherein the binding degree of the interferent prepared in comparative example 6 to miRNA is 70.8%;

wherein the degree of binding of the interferent prepared in comparative example 7 to the miRNA is 54.2%.

While the invention has been described in further detail in connection with specific embodiments thereof, it will be understood that the invention is not limited thereto, and that various other modifications and substitutions may be made by those skilled in the art without departing from the spirit of the invention, which should be considered to be within the scope of the invention as defined by the appended claims.

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