Recombinant human interferon a2b composition and application thereof

Abstract

The invention discloses a recombinant human interferon a2b composition and application thereof, and belongs to the technical field related to pharmaceutical preparations, the recombinant human interferon a2b composition comprises a therapeutically effective amount of recombinant human interferon and a luteolin clathrate compound, the active unit content of the recombinant human interferon is 1 * 10 < 6 > IU / mL to 6 * 10 < 6 > IU / mL, and the active unit content of the luteolin clathrate compound is 1 * 10 < 6 > IU / mL to 6 * 10 < 6 > IU / mL. The content of the luteolin clathrate compound is 0.2-0.8 mg / ml, the luteolin serves as an anti-allergic component and an anti-inflammatory component, anaphylaxis can be effectively reduced, propylene glycol and the luteolin are matched with each other to relieve skin inflammation and improve skin barriers, the luteolin is combined with the recombinant human interferon a2b to achieve a synergistic effect, the immunoregulation effect is achieved, and the anti-allergic effect is achieved. Replication and diffusion of viruses in cells are inhibited, and occurrence and development of herpes are reduced.

Description

Technical Field

[0001] The present invention belongs to the technical field related to pharmaceutical preparations, and in particular relates to a recombinant human interferon a2b composition and application thereof. Background Art

[0002] Recombinant human interferon a2b is an antiviral drug ingredient, mainly used as an adjuvant treatment for primary or recurrent skin herpes simplex (such as oral herpes, genital herpes) and genital warts caused by viruses. However, when recombinant human interferon a2b acts on the skin, it may cause allergic reactions, such as skin rash, itching, burning pain or redness and swelling, especially on the skin of infants and young children or patients with poor skin barriers, which has a counterproductive effect on the treatment of herpes. Scratching in children can easily lead to skin damage and inflammation. Summary of the invention

[0003] In view of the above situation, in order to overcome the defects of the prior art, the present invention provides a recombinant human interferon a2b composition and its application. Luteolin is used as an anti-allergic and anti-inflammatory ingredient to effectively reduce allergic reactions. Propylene glycol and luteolin cooperate with each other to reduce skin inflammation and improve the skin barrier. Luteolin combines with recombinant human interferon a2b to have a synergistic effect, has an immunomodulatory effect, and inhibits the replication and spread of viruses in cells, reducing the occurrence and development of herpes.

[0004] The technical solution adopted by the present invention is as follows:

[0005] In the first aspect, the present invention provides a recombinant human interferon a2b composition, comprising a therapeutically effective amount of recombinant human interferon a2b and a luteolin inclusion compound, wherein the active unit content of the recombinant human interferon a2b is 1×10 6 IU / mL~6×10 6 IU / mL; the content of the luteolin inclusion compound is 0.2-0.8 mg / ml.

[0006] Furthermore, the carrier in the luteolin inclusion compound is β-cyclodextrin, and the inclusion compound is also compounded with one or two of vitamin C and vitamin E.

[0007] In the second aspect, the present invention proposes the use of a recombinant human interferon a2b composition described in the first aspect in the preparation of preparations for treating skin herpes, oral ulcers, and hand, foot and mouth disease, wherein skin herpes includes oral herpes, herpes zoster, and genital herpes.

[0008] Furthermore, the pH value of the preparation is 6-7.5.

[0009] Furthermore, the preparation is an aerosol.

[0010] Furthermore, the aerosol is characterized in that, based on 100 ml, the aerosol formula is:

[0011]

[0012] After adopting the above scheme, the beneficial effects of the present invention are as follows: luteolin is easily dissolved in propylene glycol, and can be slowly released from the inclusion complex to act on the affected area. The two act synergistically to reduce skin inflammation and thus improve the skin barrier, making the skin easier to absorb active ingredients, and providing an action microenvironment for recombinant human interferon a2b and luteolin; recombinant human interferon a2b and luteolin inhibit the replication and spread of viruses, and have an immunomodulatory effect, enhance resistance to viruses, and effectively treat herpes while reducing recurrence. DETAILED DESCRIPTION

[0013] The technical solutions in the embodiments of the present invention will be described clearly and completely below. Obviously, the described embodiments are only part of the embodiments of the present invention, rather than all the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without making creative work are within the scope of protection of the present invention.

[0014] It should be noted that, in this article, relational terms such as first and second, etc. are only used to distinguish one entity or operation from another entity or operation, and do not necessarily require or imply any such actual relationship or order between these entities or operations. Moreover, the terms "include", "comprise" or any other variants thereof are intended to cover non-exclusive inclusion, so that a process, method, article or device including a series of elements includes not only those elements, but also other elements not explicitly listed, or also includes elements inherent to such process, method, article or device.

[0015] The methods not specifically described in the present invention are all conventional methods in the art, and the reagents not specifically described are all conventional reagents in the art.

[0016] Example 1: Preparation of luteolin inclusion compound

[0017] Luteolin, vitamin C, vitamin E and β-cyclodextrin are dissolved in a suitable solvent (such as water or ethanol), and luteolin is promoted to enter the inner cavity of β-cyclodextrin to form an inclusion complex by stirring, heating or ultrasonic treatment. Finally, the inclusion complex is obtained by evaporating the solvent or freeze drying.

[0018] The mass ratio of the total amount of luteolin, vitamin C, and vitamin E to β-cyclodextrin is 1:2; among them, the mass ratio of luteolin: vitamin C: vitamin E is 1:0.1:0.2.

[0019] Example 2: Preparation of relevant therapeutic preparations

[0020] Preparation formula: According to 100ml, prepare 1000ml preparation

[0021] Recombinant human interferon a2b 3×10 8 IU;

[0022] Luteolin inclusion complex 60mg;

[0023] Tween 80 90mg;

[0024] Propylene glycol 15 mg;

[0025] An appropriate amount of pH regulator is used to adjust the final pH of the aerosol to 6.9;

[0026] The balance is water.

[0027] Preparation of 1000 ml preparation: Accurately weigh the corresponding amount of luteolin inclusion complex, Tween 80 and propylene glycol into 800 ml of water, add the corresponding amount of recombinant interferon after dissolution, add pH regulator and water to make up to 1000 ml; after sterilization, aseptically package according to 10 ml to obtain 100 aerosols. Store at 2-8°C in the dark.

[0028] Example 3: Stability test of preparation

[0029] The above 100 preparations were stored in a refrigerator at 4°C before the test; the above material samples were divided into four batches and stored at 4-8°C, 15-20°C, 25-30°C and 37°C, respectively counted as experimental groups 1 / 2 / 3 / 4; the above four experimental groups (6-7 samples in each group) were subjected to microbial limitation, pH and appearance inspections; the test results are shown in Table 1; it can be seen from Table 1 that the preparations can be stored at 4-8°C for 12 months, the cultures of Pseudomonas aeruginosa and Staphylococcus aureus are both negative, and the counts of bacteria and molds are both less than 5.

[0030] Table 1

[0031]

[0032] Example 4: Administration route and therapeutically effective amount

[0033] The route of administration is local administration, spray on the affected area of ​​​​the skin or mucous membrane (such as oral herpes, herpes zoster, genital herpes, oral ulcers, pharyngitis, tonsillitis, hand, foot and mouth and genital warts. If the wound surface is large, it can also be sprayed multiple times to cover the entire wound surface), 2-6 sprays per area, and 3-6 times a day is recommended.

[0034] The effective amount for treatment: The appropriate dosage of the composition of recombinant human interferon a2b and luteolin may be different for different patients. The appropriate dosage is related to the administration time, duration of treatment, combined medication, severity of the disease, and the age and condition of the patient. The actual dosage is determined by the physician.

[0035] Example 5: Clinical drug research

[0036] Twenty volunteers were recruited for topical administration, during which immunomodulatory drugs, anti-inflammatory drugs, lip cosmetics, etc. were prohibited; the criteria for the subjects were as follows: clinically confirmed oral herpes and no immune system diseases, of which 6 oral herpes patients had relapsed 4-6 times within the year.

[0037] Efficacy indicators: markedly effective (pain and herpes disappeared within two days); effective (pain was relieved and symptoms were cured within 3-7 days); ineffective (pain worsened and herpes did not disappear);

[0038] Cure criteria: Scabs fall off; residual erythema may exist;

[0039] Recurrence symptoms: oral herpes, pain, erythema, papules, blisters, ulcers, swelling, etc.

[0040] The results are shown in Table 2. Combined with clinical practice, the preparation of the present application can effectively eliminate herpes labialis and effectively reduce the chance of recurrence.

[0041] Table 2

[0042]

[0043] Although the embodiments of the present invention have been shown and described, it is understood by those skilled in the art that various changes, modifications, substitutions and variations may be made to these embodiments without departing from the principles and spirit of the present invention, and the scope of the present invention is defined by the attached claims and their equivalents. In short, if those skilled in the art are inspired by it, without departing from the purpose of the invention, they can creatively design structural methods and embodiments similar to the technical solution, which should all fall within the scope of protection of the present invention. Each component of the present application can be driven by a corresponding external motor, which is a prior art and will not be elaborated in this application.

Claims

1. A recombinant human interferon a2b composition, characterized in that: Includes the following ingredients: A therapeutically effective amount of recombinant human interferon a2b and luteolin inclusion compound, wherein the active unit content of the recombinant human interferon a2b is 1×10 6 IU / mL~6×10 6 IU / mL; the content of the luteolin inclusion compound is 0.2-0.8 mg / ml.

2. The recombinant human interferon a2b composition according to claim 1 is used in the preparation of preparations for treating skin herpes, oral ulcers, and hand, foot and mouth disease, wherein skin herpes includes herpes labialis, herpes zoster, and genital herpes.

3. A recombinant human interferon a2b composition according to claim 1, characterized in that: The carrier in the luteolin inclusion compound is β-cyclodextrin, and the inclusion compound is also compounded with one or two of vitamin C and vitamin E.

4. A recombinant human interferon a2b composition according to claim 3, characterized in that: The pH value of the preparation is 6-7.

5.

5. The recombinant human interferon a2b aerosol according to claim 1, characterized in that: The preparation is an aerosol.

6. The aerosol according to claim 5, characterized in that Based on 100 ml, the aerosol formulation is: The balance is water.

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