Combination of plasma immunoglobulin and antigen- specific immunoglobulin for modification of immune system and treatment or prevention of allergic diseases

Abstract

To provide improved pharmaceutical compositions and methods for the treatment or prevention of allergic diseases.SOLUTION: The present invention provides the use of plasma immunoglobulin, such as intramuscular immunoglobulin, in combination with polyclonal antigen-specific immunoglobulin in the treatment or prevention of allergic disease. The invention furthermore provides a pharmaceutical composition comprising plasma immunoglobulin in combination with polyclonal antigen-specific immunoglobulin.SELECTED DRAWING: Figure 1A

Description

[Technical Field]

[0001] The present invention relates to the treatment of allergic diseases. In particular, the present invention relates to the prevention or In treatment, pooled immunoglobulins and antigen-specific polyclonal immunoglobulins are used. This applies to use in combination with [Background technology]

[0002] Allergic diseases afflict a significant portion of the human population and pet population. Allergen immunotherapy may be used to increase an individual's tolerance to allergens. The therapy involves two phases of allergen injections: an up-titration phase and a maintenance phase. The dose increase phase involves increasing the amount of allergen administered approximately once to three times a week for three to six months. Once an effective dose is reached, a maintenance phase may be required. However, it starts with additional injections about once every two to four weeks for several years. Both the initial and maintenance phases are quite taxing. Summary of the Invention [Problem to be solved by the invention]

[0003] The object of the present invention is to provide improved pharmaceutical compositions and methods for treating or preventing allergic diseases. The purpose is to provide

[0004] This and other objects of the present invention are achieved by reference to the detailed description of the preferred embodiments that follow. The above objectives are more than just a commitment. Please note that the above is a description of the motivation for the present invention. The present invention also includes any embodiment of the present invention described below, or the present invention as defined by each of the claims. This is not necessarily achieved through invention. [Means for solving the problem]

[0005] According to one aspect of the present invention, a combination of plasma immunoglobulins and antigen-specific immunoglobulins The combination may be used to treat or prevent allergic diseases.

[0006] In another aspect, the present invention provides a plasma immunoglobulin for the treatment or prevention of allergic diseases. This involves the use of a combination of phosphorus and antigen-specific immunoglobulin.

[0007] In another aspect, the present invention is a pharmaceutical composition for treating or preventing an allergic disease. The pharmaceutical composition comprises plasma immunoglobulin and antigen-specific immunoglobulin.

[0008] In another embodiment, the plasma immunoglobulin is intramuscular immunoglobulin.

[0009] In other embodiments, the intramuscular immune globulin is human intramuscular immune globulin.

[0010] In other embodiments, the plasma immunoglobulin is human plasma immunoglobulin.

[0011] In other embodiments, the plasma immunoglobulins are from a non-human species.

[0012] In another embodiment, the plasma immunoglobulins and the antigen-specific immunoglobulins are from the same species. It is of the type.

[0013] In another embodiment, the antigen-specific immunoglobulin is a polyclonal anti-tetanus toxoid immunoglobulin. immunoglobulin, polyclonal anti-Rh immunoglobulin, polyclonal anti-hepatitis B immunoglobulin globulin, polyclonal anti-rabies immunoglobulin, and polyclonal anti-varicella immunoglobulin The compound is selected from the group consisting of chlorine, chlorine, chlorine-containing ...

[0014] In another embodiment, the plasma immunoglobulin is greater than 50 mg / kg of body weight.

[0015] In another aspect, the present invention provides a method for injecting plasma immunoglobulins and antigen-specific immunoglobulins. The present invention relates to a method for treating or preventing an allergic disease, which method comprises administering a compound of formula (I) to a subject having an allergic disease.

[0016] In another aspect, the present invention provides a method for treating a patient comprising administering to a patient a therapeutically effective amount of plasma immunoglobulins and an aliquot of antigen-specific immunoglobulins. a kit comprising a target immunoglobulin and instructions for use, the instructions including instructions for use in treating an allergic disease; and an aliquot of plasma immunoglobulin and an aliquot of antigen-specific immunoglobulin for the treatment or prevention of a disease. A kit associated with a kit for use with Roblin.

[0017] In another aspect, the present invention provides a method for identifying a plasma immunoglobulin and an antigen-specific immunoglobulin. A kit comprising a metered amount of the mixture and instructions, the instructions including instructions for treating an allergic disease. Aliquots of plasma immunoglobulin and antigen-specific immunoglobulin for the treatment or prevention of The kit is related to the kit for use of the mixture.

[0018] The foregoing may cover only some of the aspects of the invention. Other aspects of the invention include one or more The following description of at least one preferred mode for carrying out the invention in connection with the following examples: The following aspects of the present invention can be understood by reference to: It does not define the invention itself, but is merely an example of implementing the inventive features of the present invention. [Brief explanation of the drawings]

[0019] At least one manner of carrying out the present invention in connection with several embodiments is illustrated in the following drawings: It will be explained by reference.

[0020] [Figure 1A] 1 is a graph showing that injection of IMIG in combination with polyclonal anti-tetanus toxoid Ig attenuated anti-OVA IgE responses. [Figure 1B] 1 is a graph showing that injection of IMIG in combination with polyclonal anti-tetanus toxoid Ig does not alter anti-OVA IgG responses. [Figure 1C] 1 is a graph showing OVA-induced IL-4 in splenocytes of OVA-immunized mice injected with a combination of IMIG and polyclonal anti-tetanus Ig. [Figure 1D] 1 is a graph showing OVA-induced IL-2 in splenocytes of OVA-immunized mice injected with a combination of IMIG and polyclonal anti-tetanus Ig. [Figure 2A] 1 is a graph showing OVA-induced IL-2 in splenocytes of OVA-immunized mice injected with IMIG and anti-varicella Ig. [Figure 2B] 1 is a graph showing OVA-induced IL-4 in splenocytes of OVA-immunized mice injected with IMIG and anti-varicella Ig. [Figure 3A] 1 is a graph showing the total serum IgG levels in the blood of dogs sensitized with peanut butter and prior to treatment with canine IMIG and canine anti-rabies immune Ig or prior to treatment with human IMIG and human anti-tetanus Ig. [Figure 3B] 1 is a graph showing the total serum IgG levels in the blood of dogs after sensitization with peanut butter and treatment with canine IMIG and canine anti-rabies immune Ig or human IMIG and human anti-tetanus Ig. [Figure 3C] 1 is a graph showing the overall levels of serum IgE in the blood of dogs sensitized with peanut butter and prior to treatment with canine IMIG and canine anti-rabies immune Ig or prior to treatment with human IMIG and human anti-tetanus Ig. [Figure 3D] 1 is a graph showing the overall levels of serum IgE in the blood of dogs after sensitization with peanut butter and treatment with canine IMIG and canine anti-rabies immune Ig or human IMIG and human anti-tetanus Ig. [Figure 3E] 1 is a graph showing the production of IL-2 by Con-A stimulation of dog peripheral blood lymphocytes prior to sensitization with peanut butter and treatment with canine IMIG and canine anti-rabies immune Ig or human IMIG and human anti-tetanus Ig. [Figure 3F] 1 is a graph showing the production of IL-2 by Con-A-stimulated peripheral blood lymphocytes in dogs after sensitization with peanut butter and treatment with canine IMIG and canine anti-rabies immune Ig or human IMIG and human anti-tetanus Ig. [Figure 3G] 1 is a graph showing the production of IL-4 by Con-A stimulation of dog peripheral blood lymphocytes prior to sensitization with peanut butter and treatment with canine IMIG and canine anti-rabies immune Ig or human IMIG and human anti-tetanus Ig. [Figure 3H] 1 is a graph showing the production of IL-4 by Con-A-stimulated peripheral blood lymphocytes in dogs after sensitization with peanut butter and treatment with canine IMIG and canine anti-rabies immune Ig or human IMIG and human anti-tetanus Ig. [Figure 3I] This is a graph showing the ratio of IL-2 production level / IL-4 production level due to stimulation of dog peripheral blood lymphocytes with Con-A before and after sensitization with peanut butter and treatment with canine IMIG and canine anti-rabies immune Ig or human IMIG and human anti-tetanus Ig. [Figure 3J] This is a graph showing the production of IL-2 and IL-4 by peanut butter Ag stimulating dog peripheral blood lymphocytes after sensitization with peanut butter and treatment with canine IMIG and canine anti-rabies immune Ig or human IMIG and human anti-tetanus Ig. [Figure 3K]This is a graph showing the ratio of IL-2 production level / IL-4 production level due to stimulation of dog peripheral blood lymphocytes by peanut butter Ag after sensitization with peanut butter and treatment with canine IMIG and canine anti-rabies immune Ig or human IMIG and human anti-tetanus Ig. [Figure 4A] 1 is a graph showing OVA-specific IgE serum levels in OVA-immunized mice after combined injection of various doses of IMIG and anti-tetanus Ig. [Figure 4B] 1 is a graph showing OVA-specific IgG serum levels in OVA-immunized mice after combined injection of various doses of IMIG and anti-tetanus Ig. [Figure 4C] 1 is a graph showing OVA stimulated splenocytes to produce IL-4 in OVA-immunized mice after combined injection of various doses of IMIG and anti-tetanus Ig. [Figure 4D] 1 is a graph showing OVA stimulated splenocytes to produce IL-2 in OVA-immunized mice after combined injection of various doses of IMIG and anti-tetanus Ig. [Figure 4E] 1 is a graph showing the ratio of IL-2 production level / IL-4 production level due to OVA stimulation of splenocytes in OVA-immunized mice after combined injection of various doses of IMIG and anti-tetanus Ig. DETAILED DESCRIPTION OF THE INVENTION

[0021] The pharmaceutical compositions of the present invention comprise pooled plasma immunoglobulins and antigen-specific polyclonal immunoglobulins. It is combined with Roblin.

[0022] Plasma immunoglobulins are generally prepared from the serum of at least 1000 donors and are primarily It has been used to treat patients with chronic immunodeficiency. Depending on how it is administered, it is called intramuscular immunoglobulin ("IMIG"), intravenous immunoglobulin (IVIG), or Subcutaneous immunoglobulin ("IVIG"), subcutaneous immunoglobulin ("SCIG"), intraperitoneal immunoglobulin ("IPIG"). It may be called Brin ("IPIG").

[0023] Antigen-specific polyclonal immunoglobulins are used to identify specific pathogens, such as varicella-zoster virus. or against a specific antigen such as tetanus toxoid, It is an immunoglobulin.

[0024] Combination of pooled plasma immunoglobulins and antigen-specific polyclonal immunoglobulins However, the present inventors have found that it is useful for treating or preventing allergic diseases.

[0025] As will be described in detail below, the present inventors have developed various antigen-specific antibodies against various antigens. Experiments using immunoglobulins were carried out. The antigen-specific immunoglobulins used (polyclonal antibodies) monoclonal anti-tetanus immunoglobulin, polyclonal anti-rabies immunoglobulin, polyclonal Considering the significant differences in formulation and chemical composition between the Plasma immunoglobulin can be converted to any antigen-specific immunoglobulin (polyclonal anti-Rh immunoglobulin). and polyclonal anti-hepatitis B immunoglobulins) The combination of these drugs results in a similar change in the immune system of the human or animal being treated. It is expected that allergic diseases will be similarly prevented and / or treated.

[0026] The combination of blood for the treatment and prevention of allergic diseases in humans and pets. Plasma immunoglobulin components include, but are not limited to, Gamunex® and Hiz It may be a plasma immunoglobulin approved for use in humans, such as Entra®. do.

[0027] Plasma immunoglobulins and antigen-specific polyclonal immunoglobulins may be administered in any suitable manner. For example, the antibody may be administered in a non-immunogenic manner, i.e., without an adjuvant. It may be administered in a non-immunogenic amount, for example, intramuscularly, intravenously, subcutaneously, or intraperitoneally. Pharmaceutical compositions comprising a combination of immunoglobulin and an antigen-specific polyclonal immunoglobulin The composition may be buffered saline, phosphate buffered saline, or neutral pH phosphate buffered saline. and the like, may contain a pharmaceutically acceptable carrier.

[0028] Another aspect of the invention is a method for treating a patient with a combination of an aliquot of plasma immunoglobulin and an aliquot of polyclonal antibody. Allergen-specific immunoglobulins and the role of these two different immunoglobulins in the treatment or prevention of allergic diseases and instructions for use of the aliquots.

[0029] Another aspect of the present invention is the use of plasma immunoglobulins and polyclonal antigen-specific immunoglobulins. and an aliquot of such aliquot for the treatment or prevention of allergic diseases. and instructions for use.

[0030] The antibody may be administered at any suitable site and at any suitable time. Preferably, the antibodies are administered simultaneously or substantially simultaneously. They may be administered sequentially or simultaneously, or together as a mixture. [Example]

[0031] [Example 1] Allergy experiments using polyclonal human IMIG and polyclonal human anti-tetanus Ig protocol Five BALB / c mice (8 weeks old at the start of the study) were used per group. All mice (Group 1, see below) received ovalbumin (10 μg OVA plus A l(OH)3) in 0.3 ml of phosphate-buffered saline ("PBS") on day 0. All mice were given a 14-day booster dose intraperitoneally on day 56. From day 1, the mice were given egg white solution (20% (w / v) filtered EWS) in their drinking water.

[0032] Intramuscular immunoglobulin (Gamunex® 25 μg: Grifols) The mice were treated on days 2, 7, 14, 21, 28, and 35. On the 4th and 42nd days, 0.05 ml of PBS was injected intramuscularly into the left gluteal muscle. For animals receiving immune Ig (HyperTET 25μg: Grifols) Then, on days 2, 7, 14, 21, 28, 35, and 42, 0.05 ml of PBS was injected intramuscularly into the right deltoid muscle. G or anti-tetanus was adsorbed with tetanus toxoid (x3) before use. PBS was administered only at the same site.

[0033] The following groups were used: Group 1: OVA - / EWS + Group 2: OVA + / EWS + Group 3: Group 2 + IMIG (OVA) + / EWS + +IMIG) Group 4: Group 2 + anti-tetanus Ig (OVA) + / EWS + +Anti-TetIg) Group 5: Group 2 + IMIG + anti-tetanus Ig (OVA) + / EWS + +IMIG+An ti-TetIg) Group 6: Group 2 + IMIG (treated with tetanus x3 adsorption) + anti-tetanus Ig ( OVA + / EWS + +IMIGAbs+Anti-Tet) Group 7: Group 2 + IMIG + anti-tetanus Ig (treated with tetanus x3) ( OVA + / EWS + +IMIG+Anti-Tetabs)

[0034] All mice were sacrificed on day 63 of the study. At the time of sacrifice, OVs obtained by cardiac puncture were Serum IgE against A was measured using a mouse model of OVA coated with HRP-antimacroglobulin (HRP) at 100 ng / well. The antibody was measured by ELISA using plates developed with mouse IgE and appropriate substrates. Ta.

[0035] Plus 5x10 from individual animals 6 splenocytes were in vitro treated with OVA at 1 μg / ml The cells were exposed to 2 ml of the culture medium for 72 hours, and IL-2 / IL-4 was measured using a commercially available ELISA kit ( Measurements were performed in culture supernatants using eBIOSciences.

[0036] result Figure 1A shows that the combination of IMIG and polyclonal anti-tetanus Ig resulted in a significant increase in OVA-specific Figure 1B shows that OVA-specific IgE was significantly suppressed, and Figure 1B shows that OVA-specific IgG was significantly suppressed. Referring now to Figure 1A, the adsorption of IMIG by tetanus (Group 6) and tetanus treatment with polyclonal anti-tetanus adsorption (Group 7) showed no difference. This suggests that the active pharmaceutical ingredient is not anti-tetanus antibodies.

[0037] Figure 1C shows the results for groups 5, 6, and 7, which received a combination of IMIG and anti-tetanus Ig injections. 1 shows the reduction in OVA-induced IL-4 levels in splenocytes of mice. When considered together with Figure 1D, which shows the IL-4 to IL-2 levels, the ratio of IL-4 to IL-2 was significantly higher in IMIG plus For the groups treated with anti-tetanus Ig (groups 5, 6, and 7), the control groups 2, 3, and 4 This result is clearly smaller than the alleles shown in Figures 1A and 1B. This is consistent with the suppression of ghee and its results.

[0038] [Example 2] Allergy experiments using polyclonal human IMIG and polyclonal human anti-tetanus Ig Experimental Protocol Eight BALB / c mice (8 weeks old at the start of the study) were used per group. All mice were treated with ovalbumin (10 μg OVA plus A) except for mice 1 (see below). l(OH)3) in 0.3 ml of phosphate-buffered saline ("PBS") on day 0. All mice were given 100 mg of ... The mice were fed with egg white solution (filtered 20% (w / v) EWS) at 100°C.

[0039] IMIG (Gamunex® 25 μg: Grifols) and anti-varicella Ig (25 μg: Grifols) was administered intravenously weekly from days 7 to 35. .

[0040] The following groups were used: Group 1: OVA - / EWS + Group 2: OVA + / EWS + Group 3: Group 2 + IMIG (OVA) + / EWS + +IMIG) Group 4: Group 2 + anti-varicella Ig (OVA) + / EWS + +Anti-Varicell aIg) Group 5: Group 2 + IMIG + anti-varicella Ig (OVA) + / EWS + +IMIG+Ant i-VaricellaIg)

[0041] All mice were sacrificed on day 49 of the study. At the time of sacrifice, OVs obtained by cardiac puncture were Serum IgE against A was measured using a mouse model of OVA coated with HRP-antimacroglobulin (HRP) at 100 ng / well. The antibody was measured by ELISA using plates developed with mouse IgE and appropriate substrates. Ta.

[0042] Plus 5x10 from individual animals 6 splenocytes were in vitro treated with OVA at 1 μg / ml The cells were exposed to 2 ml of the culture medium for 72 hours, and IL-2 / IL-4 was measured using a commercially available ELISA kit ( Measurements were performed in culture supernatants using eBIOSciences.

[0043] result Figure 2A shows that OVA did not attenuate IL-2 production when it stimulated individual mouse splenocytes. On the other hand, Figure 2B shows a clear attenuation of IL-4 production. The present study carried out in Example 1 using a combined infusion of IMIG and anti-tetanus Ig (See Figures 1C and 1D).

[0044] [Example 3] Polyclonal human IMIG and polyclonal IMIG were tested in peanut butter-sensitized beagle dogs. Clonal human anti-tetanus Ig, or polyclonal canine Ig and canine anti-rabies Ig were used. Allergy Experimental Protocol In a modification of the protocol in Examples 1 and 2, the inventors applied topically The prevalence of allergic sensitization induced by peanut butter spread on food is high (>80%). Previous literature reports have shown that it reduces allergic sensitization in large animals (beagles). We considered whether it would be possible to do so.

[0045] The animals received a first exposure of 1 week prior to treatment and then weekly exposure to peanut butter. The next five exposures to peanut butter were given to the combined dogs. g (IMIG and pooled canine anti-rabies Ig) or combined human Ig (IMIG and pooled human anti-rabies Ig) After 5 weeks of treatment, all animals received the same I All dogs received three more treatments with the 200 mg / kg mixture every 14 days. The subjects were orally challenged with peanut butter, and serum IgG, serum IgE, and peanut butter inducers were measured. The production of IL-2 / IL-4 by the cells was measured.

[0046] Received canine intramuscular immunoglobulin (Innovative Research, USA). The dog was given an intramuscular injection of 1 mg / kg of PBS in the gluteal muscle. Pooled canine anti-rabies immune Ig (by re-immunizing pooled dogs with rabies vaccine) 1 mg / kg of 100 mg ... Intramuscular injection was administered.

[0047] Receive human intramuscular immunoglobulin (Gamunex®, Grifols) A dose of 1 mg / kg was administered intramuscularly to the gluteal muscle of dogs using 0.5 ml of PBS as a vehicle. Dogs receiving tung Ig (HyperTET, Grifols) were injected with PBS into the gluteal muscle opposite the vena cava. 0.5 ml of the vehicle was used for intramuscular injection at 1 mg / kg.

[0048] result Figures 3A and 3B show the total serum IgG levels at the start (t0) and end (t1) of the study. Figures 3C and 3D show the results of the comparison with the total serum IgG level at time point (t1). The total serum IgE levels at the start (t0) and end (t1) of the study were The IgG level did not change significantly, but the IgE level The reduction in serum IgG levels was observed in dogs treated with canine IMIG and canine anti-rabies Ig compared with dogs treated with human IMIG and This was observed both after treatment with tetanus antibodies and with human anti-tetanus Ig.

[0049] Figures 3E and 3F show concomitant leukemia in canine peripheral blood lymphocytes (PBLs) before treatment (t0). IL-2 production by Navarin A (ConA) and the post-treatment (t1) change in canine peripheral blood lymphocytes ( Comparison of IL-2 production by concanavalin A (ConA) in PBL show.

[0050] Figures 3G and 3H show ConA-induced IL-4 production in canine PBL before treatment (t0). Comparison of ConA-induced IL-4 production in canine PBLs between fresh and post-treatment (t1) was performed. Shows.

[0051] Figure 3I shows IL-2 / IL-4 induction by ConA in canine PBL before and after Ig treatment. Even for this polyclonal response, the IL-2 / IL-4 ratio was significantly higher in dogs than in dogs with IgE. Note that the mean mean age was higher in dogs after treatment with human IgG or human IgG (*, p<0.05). I want to be done that.

[0052] Figure 3J shows the results after treatment with canine IMIG and canine anti-rabies Ig, and human IMIG and human Peanut butter stimulates canine PBL after treatment with anti-tetanus Ig. Figure 3K shows the IL-2:IL-4 ratio after treatment. Consistent with other experiments, IL-4 production was attenuated by Ig treatment, whereas IL-2 production was Furthermore, the IL-2:IL-4 ratio was higher after treatment (*, p<0.0). 5).

[0053] [Example 4] Dose-Response Study - Polyclonal Human IMIG vs Polyclonal Human in Pre-immunized Mice Anti-tetanus Ig We compared polyclonal human IMIG and polyclonal human IMIG in pre-immunized mice. A dose-response study was also performed using anti-tetanus Ig.

[0054] In the dose-response study, all groups had five BALB / c mice each. All mice were injected with OVA (10 μg O) on days 0 and 14. VA plus Al(OH3)) and boosted on day 56. All mice received From the 14th day, EWS (filtered 20% (w / v) egg white solution) was administered in a drinking container. Gave it.

[0055] Mice were injected with immunoglobulin on days 56, 63, 70, 77, and 84. Injection treatment was started.

[0056] The following groups were used: Group 1 (control): OVA immunization and EWS (No IMIG or Anti-Tet) Group 2: Group 1 + IMIG (250 μg / mouse) + anti-tetanus Ig (10 μg / mouse) (IMIG 250 :Tet 10 ) Group 3: Group 1 + IMIG (250 μg / mouse) + anti-tetanus Ig (50 μg / mouse) (IMIG 250 :Tet 50 ) Group 4: Group 1 + IMIG (250 μg / mouse) + anti-tetanus Ig (250 μg / Mouse) (IMIG 250 :Tet 250 ) Group 5: Group 1 + IMIG (50 μg / mouse) + anti-tetanus Ig (10 μg / mouse) IMIG 50 :Tet 10 ) Group 6: Group 1 + IMIG (50 μg / mouse) + anti-tetanus Ig (50 μg / mouse) IMIG 50 :Tet 50 ) Group 7: Group 1 + IMIG (50 μg / mouse) + anti-tetanus Ig (250 μg / mouse) (IMIG 50 :Tet 250 ) Group 8: Group 1 + IMIG (10 μg / mouse) + anti-tetanus Ig (10 μg / mouse) IMIG 10 :Tet 10 ) Group 9: Group 1 + IMIG (10 μg / mouse) + anti-tetanus Ig (50 μg / mouse) IMIG 10 :Tet 50 ) Group 10: Group 1 + IMIG (10 μg / mouse) + anti-tetanus Ig (250 μg / Mouse) (IMIG 10 :Tet 250 ) Group 11: Group 1 + IMIG (50 μg / mouse) + anti-tetanus Ig (50 μg / mouse) + Coenzyme Q10 ip (100 μg / mouse) from day 56 to day 90 Every 2 days (IMIG 50 :Tet 50 :Q10) Group 12: Group 1 + IMIG (250 μg / mouse) (IMIG 250 ) Group 13: Group 1 + anti-tetanus Ig (50 μg / mouse) (Anti-Tet 50 )

[0057] The final boost with OVA was on day 90 and the mice were sacrificed on day 97.

[0058] Serum OVA-specific IgG / IgE was measured by ELISA. 6 Splenocytes were exposed to 2 ml of OVA 1 μg / ml culture medium in vitro for 72 hours. IL-2 / IL-4 were cultured using a commercially available ELISA kit (BioLegend). Measured in the supernatant.

[0059] result Figures 4A and 4B show that optimal suppression of IgE responses was achieved with IMIG at 250 μg / mouse and 5 μg / mouse. 0 μg / mouse provides a wide range of anti-tetanus effects (10-250 μg / mouse) At lower doses of IMIG (10 μg / mouse), Coenzyme Q10 was administered to the animals as an antioxidant every two days (1 00 μg / mouse), a relatively small IMIG dose (50) and anti-tetanus dose At a dose of 50, there was some synergistic effect in suppression. No attenuation of the IgG response occurred. (Figure 4B).

[0060] 4C, 4D, and 4E show the results of the experiments using IL-4 and IL-2 production as measurements. This confirms the data in Figures 4A and 4B. When administered at 50 μg / mouse, it has a wide range of anti-tetanus effects (10-250 μg / mouse). ), suppression of IL-4 production was observed, but not of IL-2 production. The lower the IMIG dose (10 μg / mouse), the less suppressive the effect. The animals were given coenzyme Q10 (100 μg / mouse) every two days as an antioxidant. When administered, it was suppressed with relatively low doses of IMIG (50) and anti-tetanus (50). This data was obtained by comparing the IL-2:IL-4 ratio as shown in Figure 4E. This is further emphasized by comparison.

[0061] In the above description, exemplary modes of carrying out the present invention have been described with reference to examples. However, the scope of the claims should not be limited by the examples, but should be understood as a whole. The invention should be given the broadest interpretation consistent with the description. Therefore, the specification and drawings should not be regarded as restrictive. Rather, they are to be regarded as illustrative.

Claims

1. pooled plasma immunoglobulins comprising pooled antigen-specific immunoglobulins; and an additional antigen-specific immunoglobulin.

2. 2. The pharmaceutical composition of claim 1, wherein the additional antigen-specific immunoglobulin is selected from the group consisting of a polyclonal anti-tetanus toxoid immunoglobulin, a polyclonal anti-Rh immunoglobulin, a polyclonal anti-hepatitis B immunoglobulin, a polyclonal anti-rabies immunoglobulin, and a polyclonal anti-varicella immunoglobulin.

3. 2. The pharmaceutical composition of claim 1, wherein the pooled plasma immunoglobulin is an intramuscular immunoglobulin.

4. 4. The pharmaceutical composition of claim 3, wherein the intramuscular immunoglobulin is a human intramuscular immunoglobulin.

5. 2. The pharmaceutical composition of claim 1, wherein the pooled plasma immunoglobulin is human plasma immunoglobulin.

6. 10. The pharmaceutical composition of claim 1, wherein the pooled plasma immunoglobulins are from a non-human species.

7. 10. The pharmaceutical composition of claim 1, wherein the pooled plasma immunoglobulin and the additional antigen-specific immunoglobulin are from the same species.

8. A method of treating or preventing an allergic disease in a non-human animal comprising administering pooled plasma immunoglobulin comprising pooled antigen-specific immunoglobulin and additional antigen-specific immunoglobulin.

9. 9. The method of claim 8, wherein the antigen-specific immunoglobulin is selected from the group consisting of polyclonal anti-tetanus toxoid immunoglobulin, polyclonal anti-Rh immunoglobulin, polyclonal anti-hepatitis B immunoglobulin, polyclonal anti-rabies immunoglobulin, and polyclonal anti-varicella immunoglobulin.

10. 9. The method of claim 8, wherein the allergic disease is selected from ovalbumin allergy and peanut allergy.

11. 11. The method of claim 10, wherein the antigen-specific immunoglobulin is selected from the group consisting of polyclonal anti-tetanus toxoid immunoglobulin, polyclonal anti-Rh immunoglobulin, polyclonal anti-hepatitis B immunoglobulin, polyclonal anti-rabies immunoglobulin, and polyclonal anti-varicella immunoglobulin.

12. 9. The method of claim 8, wherein administering the pooled plasma immunoglobulin and the additional antigen-specific immunoglobulin to the non-human animal is by injection.

13. 13. The method of claim 12, wherein the injection is an intramuscular injection.

14. 2. Use of a combination of (a) pooled plasma immunoglobulin containing antigen-specific immunoglobulin and (b) additional antigen-specific immunoglobulin for the treatment or prevention of allergic disease in a non-human animal.

15. 15. The use according to claim 14, wherein the additional antigen-specific immunoglobulin is selected from the group consisting of polyclonal anti-tetanus toxoid immunoglobulin, polyclonal anti-Rh immunoglobulin, polyclonal anti-hepatitis B immunoglobulin, polyclonal anti-rabies immunoglobulin, and polyclonal anti-varicella immunoglobulin.

16. 15. The use according to claim 14, wherein the pooled plasma immunoglobulin is intramuscular immunoglobulin.

17. 17. The use according to claim 16, wherein the intramuscular immunoglobulin is a human intramuscular immunoglobulin.

18. 15. The use according to claim 14, wherein the pooled plasma immunoglobulins are human plasma immunoglobulins.

19. 15. The use according to claim 14, wherein the pooled plasma immunoglobulins are from a non-human species.

20. 15. The use according to claim 14, wherein the pooled plasma immunoglobulins and the additional antigen-specific immunoglobulin are from the same species.

21. 15. The use according to claim 14, wherein the allergic disease is selected from ovalbumin allergy and peanut allergy.

22. 1. A kit for treating or preventing an allergic disease, comprising an aliquot of pooled plasma immunoglobulins comprising pooled antigen-specific immunoglobulins, an aliquot of additional antigen-specific immunoglobulins, and instructions associated with the kit for use of the aliquot of pooled plasma immunoglobulins and the aliquot of additional antigen-specific immunoglobulins for the treatment or prevention of an allergic disease.

23. 1. A kit for treating or preventing an allergic disease, comprising: (a) a mixture of aliquots of pooled plasma immunoglobulins comprising pooled antigen-specific immunoglobulins; and (b) an additional antigen-specific immunoglobulin; and instructions for use of the mixture of aliquots of pooled plasma immunoglobulins and additional antigen-specific immunoglobulins for the treatment or prevention of an allergic disease.

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