CN113813377A

CN113813377A - Anti-alpha 4 beta 7 antibody preparation and application thereof

Info

Publication number: CN113813377A
Application number: CN202111044231.9A
Authority: CN
Inventors: 王彧; 闫天文; 王志明; 汪倩
Original assignee: Hangzhou Grand Biologic Pharmaceutical Inc
Current assignee: Hangzhou Grand Biologic Pharmaceutical Inc
Priority date: 2021-09-07
Filing date: 2021-09-07
Publication date: 2021-12-21

Abstract

The invention provides an anti- α 4 β 7 antibody preparation comprising: the composition comprises an active ingredient and an auxiliary material, wherein the active ingredient is an anti-alpha 4 beta 7 antibody, and the auxiliary material comprises at least one of the following components: sugars, free amino acids, buffers, and surfactants. The preparation of the invention has high stability, few insoluble particles in the preparation, long preservation time and simple preparation process, and is suitable for large-scale production.

Description

Anti-alpha 4 beta 7 antibody preparation and application thereof

Technical Field

The invention belongs to the field of biological medicine, and particularly relates to an anti-alpha 4 beta 7 antibody preparation and application thereof.

Background

Proteins are larger and more complex than traditional organic and inorganic drugs, not only have complex three-dimensional structures, but also have multiple functional groups, so that various factors need to be comprehensively considered in the preparation of protein drugs. In order for a protein to remain biologically active, a formulation must maintain the conformational integrity of at least one core sequence of protein amino acids while protecting the various functional groups of the protein from degradation. Proteins may suffer from a lack of stability, and monoclonal and polyclonal antibodies, in particular, may be relatively unstable. Many formulation options are available, but none of the methods or systems are suitable for all proteins. Many characteristics can affect the stability of a protein. Indeed, even in the case of purified antibodies, the antibody structure may be heterogeneous, thus further complicating the process of formulating protein preparations. In the case where the protein preparation is an antibody, it is important to maintain the conformational integrity of the antibody.

Degradation of proteins may involve chemical instability (i.e., any process that involves modification of the protein by bond formation or cleavage, thereby generating a new chemical entity) or physical instability (i.e., a higher order structural change in the protein). Chemical instability is manifested in the form of deamidation, isomerization, hydrolysis, oxidation, fragmentation, glycan beta elimination or disulfide exchange. Physical instability can be caused by denaturation, aggregation, precipitation or adsorption. The four most common protein degradation pathways are protein fragmentation, aggregation, deamidation and oxidation. The consequences of chemical or physical instability of pharmaceutically active proteins include reduced effective dosages, reduced safety of the therapy, and shorter shelf life.

In long-term clinical practice, it has been found that the insoluble particles entering the human body with the liquid during the injection of the drug can cause potential and long-term harm to the human body, for example, phlebitis, thrombosis, granuloma formation, pulmonary hypertension and the like can be induced. Therefore, attention is increasingly paid to the prevention of insoluble particles.

The anti-alpha 4 beta 7 antibody drug is a protein drug, and in the process of preparing the anti-alpha 4 beta 7 antibody preparation, how to ensure the stability of the prepared preparation is very critical.

Therefore, it is important to develop an anti- α 4 β 7 antibody preparation having high stability and few insoluble microparticles.

Disclosure of Invention

The inventors have found that current anti- α 4 β 7 antibody formulations have a variety of common side effects, such as infections and infectious diseases, immune system diseases, nervous system diseases, cardiovascular diseases, eye diseases, respiratory, thoracic and mediastinal diseases, skin and subcutaneous tissue diseases, systemic diseases and abnormalities in the site of administration; specific adverse reactions include nausea, nasopharyngitis, upper respiratory tract infections, joint pain, fever, fatigue, headache, cough, pain at infusion sites, infusion-related reactions, and the like. Through a great deal of research, the inventor finds that when the anti-alpha 4 beta 7 antibody-containing medicine is infused intravenously, the medicine needs to be redissolved before intravenous administration, and is further diluted and then administered to a patient, the interaction of various raw and auxiliary materials in a pharmaceutical preparation can influence the stability of the preparation, and certain common side effects can be related to the stability of the anti-alpha 4 beta 7 antibody preparation. The inventor also finds that after the anti-alpha 4 beta 7 antibody-containing medicament is redissolved, the formation, the number, the size and the like of insoluble particles in the preparation are influenced, particularly, the content of the insoluble particles is increased, and if the content of the insoluble particles is too high, the potential and long-term harm to a human body is caused.

To solve the above problems, in a first aspect of the present invention, the present invention provides an anti- α 4 β 7 antibody preparation. According to an embodiment of the invention, the formulation comprises: the composition comprises an active ingredient and an auxiliary material, wherein the active ingredient is an anti-alpha 4 beta 7 antibody, and the auxiliary material comprises at least one of the following components: sugars, free amino acids, buffers, and surfactants. According to the embodiment of the invention, the antibody preparation has high stability, the content of insoluble particles is obviously reduced, the safety is higher, and the preparation has a simple formula and is beneficial to production.

According to an embodiment of the present invention, the above formulation may further comprise at least one of the following additional technical features:

according to the embodiment of the invention, the mass ratio of the anti-alpha 4 beta 7 antibody to the auxiliary material is 60: (60-150); preferably, the mass ratio of the anti-alpha 4 beta 7 antibody to the auxiliary material is 60: 98, respectively; preferably, the mass ratio of the anti-alpha 4 beta 7 antibody to the auxiliary material is 60: 130.

the inventor finds that the mass ratio of the antibody to the auxiliary materials is 60: (60-150), the antibody preparation has the highest stability, can resist high temperature and vibration, has low content of insoluble particles, and has better effect than the mixture ratio of the traditional Chinese medicine preparation in other mixture ratios.

According to the embodiment of the invention, the mass ratio of the sugar, the free amino acid, the buffering agent and the surfactant is (50-110): (15-35): (1-3): (0.1-2); preferably (60-70): (20 to 30), (2 to 3), (0.3 to 1); preferably (95-105): (20-30); (2-3); (0.3 to 1). According to the embodiment of the invention, by adopting the auxiliary material proportion, the antibody preparation still has higher stability in an unstable storage environment, and the content of insoluble particles with large particle size in the antibody preparation can still be kept at a lower level when the antibody preparation is stored under a shaking condition.

According to an embodiment of the invention, the free amino acid form comprises amino acids and salts thereof, wherein the isoelectric point of the amino acid is not less than 8. The inventors have found through extensive screening and research that the use of a polar amino acid having an isoelectric point of not less than 8 as an adjuvant (e.g., arginine having an isoelectric point of 10) for an anti- α 4 β 7 antibody preparation can reduce the generation of insoluble particles in the antibody preparation, improve the stability of the antibody preparation, and reduce the damage to animals or human bodies caused by the injection of a preparation with too many particles, through the synergistic effect of the arginine and a buffer.

According to an embodiment of the invention, the free amino acid is arginine hydrochloride. According to the embodiment of the invention, the hydrochloride form of arginine is used to improve the stability of the preparation and reduce the content of insoluble particles in the preparation.

According to an embodiment of the present invention, the surfactant is a non-ionic surfactant, and further, the surfactant is polysorbate 80.

According to an embodiment of the invention, the sugar is sucrose and/or mannitol.

According to an embodiment of the invention, the pH of the formulation is 6-7, preferably 6.3. According to the embodiment of the invention, the preparation adopting the pH value has good stability, can resist the conditions of shock, high temperature and the like, and is not easy to form insoluble particles.

According to an embodiment of the invention, the formulation comprises: 50-70 mg/mL of anti-alpha 4 beta 7 antibody, 10-30 mmol/L of acetic acid/sodium acetate, 15-35 g/L of arginine hydrochloride, 90-110 g/L of sucrose and 0.1-1 g/L of polysorbate 80.

According to an embodiment of the invention, the formulation comprises: 50-70 mg/mL of anti-alpha 4 beta 7 antibody, 10-30 mmol/L of acetic acid/sodium acetate, 15-35 g/L of arginine hydrochloride, 50-110g/L of mannitol and 0.6g/L of polysorbate 80.

In a second aspect of the invention, the invention proposes the use of an anti- α 4 β 7 antibody preparation as described above in the manufacture of a medicament for the treatment or prevention of inflammatory bowel disease.

According to an embodiment of the invention, the ulcerative bowel disease is ulcerative colitis and/or crohn's disease.

In a third aspect of the invention, a pharmaceutical composition is provided. According to an embodiment of the invention, the pharmaceutical composition comprises an anti- α 4 β 7 antibody formulation as described above. According to an embodiment of the present invention, the pharmaceutical composition may further comprise other drugs for reducing inflammatory response, which may act synergistically with the antibody preparation of the present invention to achieve better or faster therapeutic effect.

Additional aspects and advantages of the invention will be set forth in part in the description which follows and, in part, will be obvious from the description, or may be learned by practice of the invention.

Detailed Description

The following detailed description of the embodiments of the present invention is intended to be illustrative, and not to be construed as limiting the invention.

Antibody formulations

Herein, the term "antibody" is an immunoglobulin molecule capable of binding to a specific antigen. Comprises two light chains with lighter molecular weight and two heavy chains with heavier molecular weight, wherein the heavy chains (H chains) and the light chains (L chains) are connected by disulfide bonds to form a tetrapeptide chain molecule. Among them, the amino-terminal (N-terminal) amino acid sequence of the peptide chain varies widely and is called variable region (V region), and the carboxy-terminal (C-terminal) is relatively stable and varies little and is called constant region (C region). The V regions of the L chain and H chain are referred to as VL and VH, respectively.

Certain regions in the variable region, which have a higher degree of variation in amino acid composition and arrangement order, are called Hypervariable regions (HVRs), which are the sites where antigens and antibodies bind and are therefore also called complementarity-determining regions (CDRs). The heavy chain variable region and the light chain variable region both have three CDR regions.

According to the invention, the anti-alpha 4 beta 7 antibody is compounded with free amino acid, non-reducing sugar and surfactant, and through a large number of experiments, the anti-alpha 4 beta 7 antibody preparation with high stability, strong biological activity and long storage time is finally obtained by screening.

In a first aspect of the invention, the invention features an anti- α 4 β 7 antibody formulation. According to an embodiment of the invention, the formulation comprises: the anti-alpha 4 beta 7 antibody-containing active ingredient comprises an active ingredient and an auxiliary material, wherein the active ingredient is an anti-alpha 4 beta 7 antibody, and the auxiliary material comprises: selected from at least one of: sugars, free amino acids, buffers, and surfactants. The formulations can reduce deamidation, oxidation, isomerization and/or aggregation of the anti- α 4 β 7 antibody, and improve stability of the antibody.

"stable" is the ability of an antibody to retain its physical properties and/or its chemical properties and/or its biological activity when stored.

By "reducing deamidation, oxidation, aggregation, or fragmentation" is meant preventing or reducing the amount of deamidation, aggregation, or fragmentation relative to an antibody formulated at a different pH or in a different buffer.

An "insoluble microparticle" is more than ten antibody proteins and/or fragments that associate together by covalent, ionic, or hydrophobic interactions to form a larger protein body.

In some embodiments, the sequence of the anti- α 4 β 7 antibody. The antibody can be a full-length antibody or an antigen-binding fragment thereof. The antibodies have conservative amino acid substitutions compared to the amino acid sequences described above. An "antigen-binding fragment" refers to an antibody fragment that retains the ability to specifically bind to an antigen. "conservative amino acid substitution" refers to the replacement of an amino acid by another amino acid residue that is biologically, chemically, or structurally similar. Biologically similar means that the substitution does not destroy the biological activity of the anti- α 4 β 7 antibody or with the anti- α 4 β 7 antigen. Structurally similar refers to amino acids having side chains of similar length, such as alanine, glycine, or serine, or side chains of similar size. Chemical similarity refers to amino acids that are identically charged or are both hydrophilic or hydrophobic. For example, the hydrophobic residues isoleucine, valine, leucine or methionine. Or a polar amino acid such as lysine by arginine, aspartic acid by glutamic acid, asparagine by glutamine, threonine by serine, and the like.

Full-length antibodies are antibodies comprising an antigen-binding variable region and a light chain constant domain (CL) and heavy chain constant domains CH1, CH2, and CH 3. The constant domain may be a native sequence constant domain (e.g., a human native sequence constant domain) or an amino acid sequence variant thereof. Full-length antibodies have one or more effector functions.

In some embodiments, the antibody preparation can contain any one desired free amino acid, which can be in the L-form, D-form, or any desired mixture of these forms, such as histidine, alanine, arginine, glycine, glutamic acid, serine, lysine, tryptophan, valine, cysteine, and combinations thereof.

In some embodiments, the antibody formulation contains at least one surfactant that can control soluble and insoluble aggregate formation.

In some embodiments, the mass ratio of the anti- α 4 β 7 antibody to the adjuvant is 60: (60-150).

In some embodiments, the mass ratio of the anti- α 4 β 7 antibody to the adjuvant is 60: 98.

in some embodiments, the mass ratio of the anti- α 4 β 7 antibody to the adjuvant is 60: 130.

the antibody and the auxiliary materials have better stability when being mixed according to the proportion.

In some embodiments, the mass ratio of the sugar, the free amino acid, the buffer and the surfactant is (50-110): (15-35): (0.5-3): (0.1-2); preferably (60-70): (20 to 30), (0.5 to 2), (0.3 to 1); preferably (95-105): (20 to 30), (0.5 to 2), (0.3 to 1). According to the embodiment of the invention, by adopting the auxiliary material proportion, the antibody preparation still has higher stability in an unstable storage environment, and the content of insoluble particles with large particle size in the antibody preparation can still be kept at a lower level when the antibody preparation is stored under a shaking condition.

In some embodiments, the SEC mer peak area is no greater than 26.2 with 10 days of illumination; at a high temperature of 10 days, the SEC polymer peak area is not higher than 0.8. The preparation has high stability, less insoluble particles, and reduced aggregate formation during storage and transportation.

Pharmaceutical application and pharmaceutical composition

The anti- α 4 β 7 antibody formulations provided herein can be incorporated into pharmaceutical compositions suitable for administration to a subject. Typically, these pharmaceutical compositions include the anti- α 4 β 7 antibody formulations provided herein, as well as other pharmaceutically acceptable carriers. "pharmaceutically acceptable carrier" can include any and all solvents, dispersion media, coatings, antibacterial and antifungal agents, isotonic and absorption delaying agents, and the like, that are physiologically compatible. Of course, the pharmaceutically acceptable carrier may also include minor amounts of auxiliary substances, such as wetting or emulsifying agents, preservatives.

For example, the antibodies of the invention can be incorporated into pharmaceutical compositions suitable for parenteral administration (e.g., intravenous, subcutaneous, intraperitoneal, intramuscular). These pharmaceutical compositions can be prepared in various forms. Such as liquid, semi-solid, and solid dosage forms, and the like, including, but not limited to, liquid solutions (e.g., injectable and infusible solutions), dispersions or suspensions, tablets, pills, powders, liposomes, and suppositories. Typical pharmaceutical compositions are in the form of injection solutions or infusion solutions. The antibody may be administered by intravenous infusion or injection or intramuscular or subcutaneous injection.

In some embodiments, the ulcerative bowel disease is ulcerative colitis and/or crohn's disease.

In the treatment of the above-mentioned diseases using the anti- α 4 β 7 antibody preparation provided by the present invention, the anti- α 4 β 7 antibody preparation provided by the present invention may be provided to a subject.

In a third aspect of the invention, a pharmaceutical composition is provided. According to an embodiment of the invention, the pharmaceutical composition comprises an anti- α 4 β 7 antibody formulation as described above.

The invention will now be described with reference to specific examples, which are intended to be illustrative only and not to be limiting in any way.

EXAMPLE 1 preparation of antibody formulations

1. Preliminary screening of formulation

(1) Prescription screening condition 1 (18 groups of conditions including buffer solution system, pH and free amino acid species) comprises active ingredient concentration of 60mg/ml, sucrose of 100g/L, and polysorbate 80 of 0.6 g/L;

a buffer system is 1:20mmol/L acetic acid/sodium acetate;

a buffer system 2 of 10mmol/L citric acid/sodium citrate;

the pH value is 5.8, 6.3 and 6.8;

free amino acids including arginine, alanine, and glycine.

(2) Prescription screening condition 2 (16 groups of conditions with changed non-reducing sugar ratio) comprises active ingredient concentration of 60mg/ml, histidine of 50mmol/L, arginine of 26.34g/L, polysorbate 80 of 0.6g/L, and pH of 6.3;

the non-reducing sugar is 1: mannitol, and the final concentration is 68g/L, 82g/L, 100g/L and 118 g/L;

sorbitol is used as the non-reducing sugar 2, and the final concentration is 68g/L, 82g/L, 100g/L and 118 g/L;

non-reducing sugar 3: sucrose, the final concentration is 68g/L, 82g/L, 100g/L and 118 g/L;

non-reducing sugar 4 trehalose dihydrate, the final concentration is 68g/L, 82g/L, 100g/L, 118 g/L.

(3) Prescription screening condition 3 (removing or changing single component of original prescription, 4 groups of conditions) comprises active ingredient concentration of 60mg/ml and pH of 6.3;

condition one (histidine removed) arginine 26.34g/L, polysorbate 80 0.6g/L, sucrose 100 g/L;

condition two (arginine removal), sucrose 100g/L, polysorbate 80 0.6g/L, histidine salt 50 mmol/L;

condition three (removing polysorbate 80), arginine 26.34g/L, sucrose 100g/L, histidine salt 50 mmol/L.

Setting the active components of the anti-alpha 4 beta 7 antibody unchanged, and carrying out orthogonal experiments to obtain 38 groups of experimental conditions; and respectively carrying out parallel experiments on the 38 groups of experimental samples with influence factors such as freeze thawing, high temperature, illumination and the like.

As a result: by comprehensively evaluating the polymer content and SEC/IEX key index results in each preparation prescription, the basic buffer system of the preparation can be preliminarily confirmed to be an acetic acid/sodium acetate buffer system. The inventor finds that the citric acid/sodium citrate buffer system is not suitable, and milky turbid sediment is generated when a sample is prepared; the free amino acid can be alanine and arginine hydrochloride, and the pH value is preferably 5.8-6.3; sucrose and mannitol are superior to the other two non-reducing sugars.

2. Formulation screening and design

(1) Prescription screening condition 1 (free amino acid, sucrose concentration, pH value range, total 18 prescriptions):

active ingredient concentration: 60mg/ml, polysorbate 80(PS 80): 0.6g/L, 20mmol/L acetic acid/sodium acetate;

free amino acids: alanine, arginine hydrochloride (concentration: 26.34 g/L);

the sucrose concentration: 68g/L, 82g/L and 100 g/L;

pH value: 5.5, 5.8 and 6.3.

Table 1 recipe screening conditions 1

(2) Prescription screening condition 2 (18 prescriptions in total, wherein sucrose is replaced by mannitol in prescription screening condition 1, and other design conditions are consistent):

the concentration of active ingredients is 60mg/ml, the concentration of free amino acid is 26.34g/L, the concentration of polysorbate 80 is 0.6g/L, and the concentration of acetic acid/sodium acetate is 20 mmol/L;

free amino acids: alanine, arginine hydrochloride (concentration: 26.34 g/L);

concentration of mannitol: 68g/L, 82g/L and 100 g/L;

pH value: 5.5, 5.8 and 6.3.

Table 2 prescription screening conditions 2

(3) Prescription screening condition 3 (replacement of non-reducing sugar to mannitol):

the concentration of active ingredients is 60mg/ml, arginine hydrochloride is 26.34g/L, mannitol is 82g/L, acetic acid/sodium acetate is 20mmol/L, polysorbate 80 is 0.6g/L, and the pH value is 5.8.

TABLE 3 prescription screening Condition 3

(4) Prescription screening condition 4 (12 sets of conditions were used in total, except that sorbitol was replaced with sucrose in prescription screening condition 1):

active ingredient concentration: 60mg/ml, PS80:0.6g/L, 20mmol/L acetic acid/sodium acetate;

free amino acids including alanine and arginine hydrochloride (concentration: 26.34 g/L);

sorbitol concentration is 68g/L and 82 g/L;

the pH value is 5.5, 5.8 and 6.3.

Table 4 prescription screening conditions 4

Example 2 high temperature, high humidity stability test

1. Investigation of high temperature test

The 49 groups of samples are respectively subjected to high temperature and illumination influence factor tests, and the stability conditions of the 49 groups of samples with different prescriptions in a liquid state are examined. From the first round of screening experiment results, the samples are sensitive to the illumination condition, and the experiment of the round is firstly carried out under the high-temperature condition for 5 days and then the illumination factor is considered. Experimental samples the SEC/IEX-UPLC/HPLC detection results after being placed for 5 days in the high temperature test are shown in Table 5.

TABLE 5 high temperature SEC/IEX test results

According to table 5 influencing factors: and (3) analyzing the detection result after being placed at a high temperature for 5d, wherein 9 sample conditions such as serial numbers of 16-18, 34-37, 48 and 49 are superior to those of other prescription experiment condition samples, compared with other prescription experiment condition samples, the SEC polymer peak areas of the 9 samples are lower, and meanwhile, the main peak area of IEX is higher, namely, the SEC polymer peak areas are less than or equal to 0.9, and the main peak area of IEX is greater than 55. Subsequent experiments further stability confirmation was performed on the 9 prescriptions determined in the first experimental screening.

2. Investigation of high temperature and light test

The high temperature and light exposure test was continued through the 9 experimental samples identified above, and the SEC/IEX-UPLC/HPLC test results on day 10 are shown in Table 6.

TABLE 6 SEC/IEX test results of high temperature and light test

According to the SEC/IEX-UPLC/HPLC detection result analysis of the table 6, the influence factors are placed at high temperature for 10 days, the detection results of 6 groups of experiment condition samples with serial numbers of 16-18, 34-36 and the like are basically consistent, the peak area of the polymer is not higher than 0.8, and meanwhile, the main peak area is larger than 51; the light condition is a sensitive factor, and the peak area of the polymer is not higher than 27 under parallel comparison.

Example 3 Freeze drying influential factor assay

In a liquid state, 6 groups of experiment conditions such as serial numbers 16-18, 34-36 and the like are better, and finally, the 6 groups of experiment condition samples are selected to carry out the last dosage form freeze-drying process exploration and the prescription stability confirmation after freeze-drying.

TABLE 7 SEC/IEX detection results of reconstituted samples after lyophilization

After the samples of the 6 groups of experimental conditions are redissolved in a freeze-dried state, the detection data in the table 8 are comprehensively analyzed and evaluated, and in the samples No. 18 and No. 34, the peak area of a polymer is not higher than 0.8, and meanwhile, the main peak area is larger than 69. Obviously, samples No. 18 and No. 34 are superior to other groups, and finally the formulations are determined to be No. 18 (20mmol/L acetic acid/sodium acetate, pH6.3, arginine: 26.34g/L, sucrose: 100g/L, PS80:0.6 g/L) and No. 34 (20mmol/L acetic acid/sodium acetate, pH6.3, arginine hydrochloride: 26.34g/L, mannitol: 68g/L, PS80:0.6 g/L).

Example 4 shaking test

TABLE 8 results of the shock test

The inventors performed a concussion test under the same conditions as the samples No. 18 and No. 34 by using a commercially available anti- α 4 β 7 antibody drug as a control group. Table 8 shows that after 20 days of shaking, the insoluble particles with the particle sizes of 10 μm or more and 25 μm or more in samples No. 18 and No. 34 are obviously smaller than those in the control group, which indicates that the stability of the insoluble particles under the conditions of the prescriptions No. 18 and No. 34 is obviously better than that of the prescriptions in the control group.

In the description herein, references to the description of the term "one embodiment," "some embodiments," "an example," "a specific example," or "some examples," etc., mean that a particular feature, structure, material, or characteristic described in connection with the embodiment or example is included in at least one embodiment or example of the invention. In this specification, the schematic representations of the terms used above are not necessarily intended to refer to the same embodiment or example. Furthermore, the particular features, structures, materials, or characteristics described may be combined in any suitable manner in any one or more embodiments or examples. Furthermore, various embodiments or examples and features of different embodiments or examples described in this specification can be combined and combined by one skilled in the art without contradiction.

Although embodiments of the present invention have been shown and described above, it is understood that the above embodiments are exemplary and should not be construed as limiting the present invention, and that variations, modifications, substitutions and alterations can be made to the above embodiments by those of ordinary skill in the art within the scope of the present invention.

Claims

1. An anti- α 4 β 7 antibody formulation comprising: the composition comprises an active ingredient and an auxiliary material, wherein the active ingredient is an anti-alpha 4 beta 7 antibody, and the auxiliary material comprises at least one of the following components: sugars, free amino acids, buffers, and surfactants.

2. The preparation of claim 1, wherein the mass ratio of the anti- α 4 β 7 antibody to the adjuvant is 60: (60-150);

preferably, the mass ratio of the anti-alpha 4 beta 7 antibody to the auxiliary material is 60: 98, respectively;

preferably, the mass ratio of the anti-alpha 4 beta 7 antibody to the auxiliary material is 60: 130.

3. the preparation according to claim 1, wherein the mass ratio of the sugar, the free amino acid, the buffer and the surfactant is (50-110): (15-35): (1-3): (0.1-2); preferably (60-70): (20-30) and (2-3): (0.3 to 1); preferably (95-105): (20-30): (2-3): (0.3 to 1).

4. The formulation of claim 1, wherein the free amino acid form comprises an amino acid and salts thereof, wherein the amino acid has an isoelectric point of not less than 8.

5. The formulation of claim 4, wherein the free amino acid is arginine hydrochloride.

6. The formulation of claim 1, wherein the surfactant is polysorbate 80.

7. The formulation according to claim 1, characterized in that the sugar is sucrose and/or mannitol.

8. The formulation according to claim 1, wherein the formulation has a pH of 6 to 7, preferably 6.3.

9. A formulation according to any one of claims 1 to 8, comprising: 50-70 mg/mL of anti-alpha 4 beta 7 antibody, 10-30 mmol/L of acetic acid/sodium acetate, 15-35 g/L of arginine hydrochloride, 50-110g/L of sucrose and 0.1-1 g/L of polysorbate 80.

10. A formulation according to any one of claims 1 to 8, comprising: 50-70 mg/mL anti-alpha 4 beta 7 antibody, 10-30 mmol/L acetic acid/sodium acetate, 15-35 g/L arginine hydrochloride, 50-110g/L mannitol and 0.1-1 g/L polysorbate 80.

11. An anti- α 4 β 7 antibody formulation comprising: 60mg/mL anti- α 4 β 7 antibody, 20mmol/L acetic acid/sodium acetate, 26.34g/L arginine hydrochloride, 100g/L sucrose, and 0.6g/L polysorbate 80.

12. An anti- α 4 β 7 antibody formulation comprising: 60mg/mL anti-alpha 4 beta 7 antibody, 20mmol/L acetic acid/sodium acetate, 26.34g/L arginine hydrochloride, 68g/L mannitol and 0.6g/L polysorbate 80.

13. Use of an anti- α 4 β 7 antibody preparation according to any one of claims 1 to 8, 11 to 12 in the manufacture of a medicament for the treatment or prevention of inflammatory bowel disease, preferably ulcerative colitis and/or crohn's disease.

14. A pharmaceutical composition comprising an anti- α 4 β 7 antibody preparation according to any one of claims 1 to 8 and 11 to 12.