JP2978432B2 - Pharmaceutical composition for reducing antinuclear antibody and pharmaceutical composition for reducing rheumatoid factor - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

The present invention relates to a pharmaceutical composition for reducing antinuclear antibodies and a pharmaceutical composition for reducing rheumatoid factor.

[0002]

2. Description of the Related Art SLE (Systematic Lup)
autoimmune diseases such as erythematosus (us Erythematosus), malignant rheumatoid arthritis, Behcet's disease, scleroderma, dermatomyositis and polymyositis, idiopathic thrombocytopenic purpura, and ulcerative colitis. It is considered one of the difficult incurable diseases. This SLE
Although autoimmune diseases such as those presenting various symptoms, there is pain such as joint disease among them, and conventionally only anti-inflammatory analgesics and vitamins are administered, and the sufficient therapeutic effect has not been raised. It is the current situation.

[0003]

DISCLOSURE OF THE INVENTION The present invention has been made to overcome such a situation, and has as its object to provide a pharmaceutical composition for reducing antinuclear antibodies and a pharmaceutical composition for reducing rheumatoid factor. .

[0004]

In order to achieve the above-mentioned object, the pharmaceutical composition for reducing antinuclear antibodies and the pharmaceutical composition for reducing rheumatoid factor according to the present invention are characterized in that they comprise a thymus of a mammal as a main component. I do.

[0005] The thymus of mammals has an analgesic effect,
It is known from the study of the present inventors that taking a composition containing the thymus as a main component has an analgesic effect on arthritis and the like due to rheumatism and the like.
No. 63 and the like. In this study of the thymus, the present inventors have found that the thymus of mammals not only has an analgesic effect, but also has an effect of reducing antinuclear antibodies in patients with systemic lupus erythematosus and a decrease in rheumatoid factors in patients with malignant rheumatoid arthritis and the like. We came to the finding that it was effective. Thus, the compositions according to the invention are useful for systemic lupus erythematosus, malignant rheumatoid arthritis, Behcet's disease,
It is effective for autoimmune diseases such as scleroderma, dermatomyositis and polymyositis, idiopathic thrombocytopenic purpura, and ulcerative colitis.

[0006] Antinuclear antibody (antinuclear factor
r) is an autoimmune antibody against intracellular nuclear material and is present in the blood of many autoimmune disease patients, including systemic lupus erythematosus (systemic lupus erythematosus). Therefore, it is important for diagnosis and classification of these diseases, estimation of prognosis, and determination of treatment. For detection of an antinuclear antibody, an indirect fluorescent antibody method is usually used. As a nuclear material as an antigen, rat hepatocytes, peripheral leukocytes, chicken erythrocytes, cultured cells and the like are used. Specifically, the cells are spread on a slide glass, dried and fixed, and then one drop of the test serum is dropped. After leaving it at room temperature for 30 minutes, it is washed with water, and a fluorescent dye-labeled anti-human γ globulin rabbit serum is added dropwise. After leaving at room temperature for 30 minutes, wash with water,
Enclose with glycerin and observe with a fluorescence microscope. The maximum dilution of the positive serum is defined as the antinuclear antibody titer. The LE cell test which has been known for a long time is also one of the antinuclear antibody detection methods. In this method, blood collected from a patient is left at room temperature, and after coagulation, a blood clot is rubbed with a wire mesh, and a leukocyte layer is separated from the blood thus obtained. After smearing the slide glass, it is stained with Giemsa and observed with a microscope. Neutrophils that phagocytosed a circular inclusion (LE body) slightly larger than the nucleus stained with fluorescent dye
They are called cells. If this is found, the LE phenomenon becomes positive. The antinuclear antibody that causes this is called LE factor and is an IgG class antibody against the protein. Looking at the antinuclear antibody positive rate in each disease, 80-100% for SLE, 5-23% for systemic sclerosis (PPS), rheumatoid arthritis (R
A) 5-17%, autoimmune hepatitis (AH) 15-3%
0%, 20 with Sjogren's syndrome
It is said to be ~ 50%. In the indirect fluorescent antibody method, 75-100% for SLE and 30-100% for PSS
%, RA is 10-36%, AH is 50-73%, and Sjogren's syndrome is 60-70%.

[0007] Rheumatoid (rheumatoid) factor is found in 70-80% of the sera of patients with rheumatoid arthritis, is an autoantibody to the Fc portion of IgG, and is thought to be closely related to the disease state. Clinically detected by RA test and RAHA test are Ig with high aggregation ability
M-class rheumatoid factor, in addition to IgG, Ig
A, there are also rheumatoid factors of the IgE class. In addition to rheumatoid arthritis, it is known that the positive rate is high in so-called collagen diseases such as systemic lupus erythematosus, chronic liver diseases, and subacute bacterial endocarditis.

The present invention is based on the above findings, and the pharmaceutical composition for reducing an antinuclear antibody and the pharmaceutical composition for reducing a rheumatoid factor of the present invention mainly contain a thymus of a mammal. If necessary, calcium, wheat germ, excipients and the like may be added. As the thymus of mammals, thymus of cows, sheep, pigs, and the like can be generally used, and calves are appropriate in terms of supply. Also, the mature thymus of those mammals can be used, but those prior to maturity are preferred. The thymus is preferably subjected to a hot water treatment at 60 ° C. for 20 to 30 minutes after grinding the raw material thymus, followed by drying by freeze-drying and sieving to use as a powder.

It is possible to add one or more of barley extract, sansho extract, quince extract and licorice extract which have an analgesic effect to the above-mentioned components. It is also possible to add one or more of the following components: the perfume extract, the chicken blood wister extract, the Keishi extract, the safflower extract, and the Kaikei ground yellow tea powder. It is also possible to add one or more of calcium, vitamin B group and vitamin E. These additives may be added in combination or may be added alone to the thymus.

[0010] For barley, sansho, gokahi, matsuba, licorice, incense, chicken blood wisteria, Keishi, and safflower, each dried material is finely cut and simultaneously extracted with a 30% ethanol solution. After removing contaminants with a centrifugal separator, the resultant was dried by spray drying (spray drying), and the resulting solid was pulverized and sieved to obtain a dry extract powder. Huaiqing ground yellowish tea powder is obtained by washing and sorting the collected "ground yellow" tubers, drying in the sun, milling to a size of 200 to 100 mesh, and drying and sterilizing at 100 degrees Celsius for 10 to 15 minutes. Powdered tea. Calcium, thiamine nitrate (vitamin B1), riboflavin (vitamin B2), pyridoxine hydrochloride (vitamin B6), cyanocobalamin (vitamin B12), and tocopherol (vitamin E) are products that meet specified quality standards from raw material suppliers. Purchase and use as compounding material.

If the composition and effectiveness of each of the above-mentioned compounding materials are shown,
It is as follows. <Group 1> Adlay extract: fatty oil / coioxol C ₈ H ₇ O ₃ N, stero
It contains l, amino acid, vitamin B1, etc., and is considered to have analgesic, antispasmodic and debilitating effects in Oriental medicine such as Chinese medicine and Chinese medicine in addition to water irrigation and antiviral effects, and is particularly effective for neuralgia. Sansho extract: 2-4% of essential oil, α-sanshol C ₁₆ H ₂₇ O
It contains N, sanshoamide C ₁₆ H ₂₅ O ₂ N, tannin, etc., and has an analgesic effect, especially a neuralgia, in addition to stomachic and detoxification. Goka Skin Extract: Contains essential oils, vitamins A and B, supplements the liver and kidneys, strengthens muscle bones, has anti-inflammatory effects, eliminates edema, and has other analgesic effects, and is a prescription combination for rheumatoid arthritis and arthralgia. Used for Pine needle extract: contains a lot of essential oils, oriental medicine improves insomnia,
It is said to have an analgesic effect such as joint pain and a sedative effect. Licorice extract: Contains a large amount of glycyrrhizin, has other analgesic and sedative effects such as spleen benefit, detoxification and detoxification, and has the function of harmonizing the whole ingredients. <Group 2> Fragrance extract: Contains a lot of essential oils, and has effects such as sedation, vitality and the like. Niwatorichifuji _{Extract: milletol C 29 H 50 O 2} , including iron, addition to analgesia to improve circulation state by improving blood flow, limb atrophy, numbness, is effective in such paralysis. Keishi _{extract: cinnamic aldehyde C 9 H 80,} cinnamoyl e
It contains thyl acetate and the like, and has analgesic effects such as antipyretic, confounding, stomachic, antibacterial, antiviral, and antifungal activities, and in particular, headache caused by vasospasm of the head. Safflower _{Extract: carthamin C 21 H 22 O 11} , saflor yel
It contains low C ₂₄ H ₃₅ O ₅ and has the effects of improving blood flow, confounding, etc., and is effective for pain due to menstrual pain, angina pain, bruise, sprain, bruise, etc., internal bleeding, and swelling. Kaikei ground yellow tea tea powder: including sitosterol, D-mannitol, iridoi glycoside catalpol, etc.
Diuretic, nourishing tonic. <Group 3> Calcium: Calcium has a sedative effect by stabilizing the nervous system and, consequently, an effect of reducing pain sensation. Thiamine nitrate (vitamin B1): It has the effect of suppressing neuralgia and numbness of limbs. Riboflavin (vitamin B2): immunostimulatory action, skin
It has an anti-inflammatory effect as well as a protective effect on mucous membranes. Inflammation is also one of the major causes of pain, including the case of arthritis, and its analgesic effect is expected by suppressing inflammation. Pyridoxine hydrochloride (vitamin B6): has the effect of normalizing the functions of the skin, mucous membranes and nerves, and is expected to have the effect of suppressing excessive reactions of painful nerves. Cyanocobalamin (vitamin B12): has an action to relieve pain in peripheral nerves. Tocopherol (vitamin E): has the effect of promoting blood circulation and suppressing the generation of lipid peroxide. Poor blood circulation is one of the causes of pain, and in that case, it is said that the improvement in blood circulation will relieve the pain. Also, it is said that free radicals such as lipid peroxide play a large role in the development and progression of inflammation. Therefore, by suppressing the generation and inflammation of lipid peroxide, prevention of pain and analgesic effects are expected.

It is desirable that the content of each of these components is in the following range. <Group 1> Barley extract: 6 wt% or more and 24 wt% or less Sansho extract: 1.2 wt% or more and 4.8 wt% or less Gokahi extract: 5 wt% or more and 20 wt% or less Matsuba extract: 4.0 wt% or more and 16.0 wt% or less Licorice extract: 2.3 wt% or more and 9.2 wt% or less <Group 2> Fragrance extract: 2.5 wt% or more and 10 wt% or less Chicken blood wister extract: 5 wt% or more and 20 wt% or less Keishi extract: 2.5 wt% or more and 10 wt% % Or less Safflower extract: 2.5% by weight or more and 10% by weight or less Kaikei ground yellow tea powder: 4.7% by weight or more and 19% by weight or less <Group 3> Calcium: 0.6% by weight or more and 2.7% by weight or less Thiamine nitrate (vitamin B1) : 1.7 wt% or more and 6.8 wt% or less Riboflavin (vitamin B2): 3.4 wt% or more 13 6 wt% or less Pyridoxine hydrochloride (vitamin B6): 3.4 wt% or more and 13.6 wt% or less Cyanocobalamin (vitamin B12): 0.00003 wt% or more and 0.00012 wt% or less Tocopherol (vitamin E): 1.4 wt% or more 5 0.6wt% or less

[0013]

Next, an embodiment will be described. The composition of the present invention of the following components is kneaded and compacted into tablets of 450 mg per tablet, and administered to patients of the following cases 1 to 4, and as a result, the antinuclear antibody lowering effect or RF (rheumatic factor) as shown below is obtained. The effect of lowering was obtained. Calf thymus powder: 21.8 wt% Sansho extract: 2.4 wt% Adlay extract: 11.2 wt% or more Gokahi extract: 10.3 wt% Matsuba extract: 5.5 wt% Licorice extract: 4.6 wt% Perfume extract: 4.6 wt% Chicken blood wister extract: 9.5 wt% Keishi extract: 4.6 wt% Safflower extract: 4.6 wt% Kaikei ground yellowish tea powder: 4.9 wt% Calcium: 0.8 wt% Thiamine nitrate (vitamin B1 ): 3.4 wt% Riboflavin (vitamin B2): 4.0 wt% Pyridoxine hydrochloride (vitamin B6): 4.0 wt% Cyanocobalamin (vitamin B12): 0.00007 wt% Tocopherol (vitamin E): 2.7 wt%

<Case 1> 42-year-old female Chief complaint: precordial pain, bilateral knee arthritis Current medical history: From around March 1991, the above symptoms were accompanied by a fever of the 37 ° C. range. I consulted.
There was tenderness in the third to sixth ribs on the left side, and there were no radiological findings. She was diagnosed with Tietzse syndrome and prescribed analgesics and muscle relaxants, but her pain was not improved. Since gastrointestinal dysfunction was caused by oral medication, the progress was monitored only with topical drugs and compresses from July of the same year. Of the pain, precordial pain disappeared, but both knee joint pain persisted, so RA was suspected and various tests were performed. As a result, the antinuclear antibody was 4
Since it was 0-fold and positive, the composition of the present invention was administered for 6 days a day from the end of February 1992 under the diagnosis of systemic lupus erythematosus.
Administration of the tablets was started. As a result, the antinuclear antibody decreased as follows. After that, the symptoms gradually resolved, and disappeared completely at the time of consultation in early April of the same year. Inspection results: Item normal value H4 February H4 April H4 October October RF <40 19.5 19.8 21.0 LE test (-) (-) () (-) Antinuclear antibody <20 40 (Homo) 20 or less 20 or less anti-ss-DNA antibody <2 1.5 0.4 1.0 anti-ds-DNA antibody <2 1.0 0.5 0.9 CRP <0.3 0.07 0.07 0.07

<Case 2> Female, 20 years old, chief complaint: bilateral knee joint pain, precordial pain Current medical history: bilateral knee joint pain since June 1985, pain worsened during exercise and when sitting straight. He received electrotherapy at the osteopath in November of the same year, but did not improve. He was consulted at the National Hospital Orthopedic Surgery in February 1986. His findings at the time of the visit were marked as "the opposite knee" and tenderness on the medial side of the knee. Os
He was diagnosed as having good disease and knee distention, and was temporarily relieved after receiving topical drugs. From late October 1992, she suffered from both knee joint pain and precordial pain again.
Tenderness was found in the anterior border of the sternum, and various examinations revealed a diagnosis of systemic lupus erythematosus. The patient was treated with anti-inflammatory analgesics and vitamin B6 and vitamin B12, but the pain did not improve.
From the beginning of January, the above-mentioned composition of the present invention was administered in 6 tablets daily. As a result, a test in late November of the same year showed a significant decrease in antinuclear antibodies. Test result: Item normal value H4 October H4 November November RF <40 21.0 19.5 LE test (-) (-) (-) Antinuclear antibody <20 320 (homo) 160 (homo) anti-ss -DNA antibody <2 2.0 1.4 anti-ds-DNA antibody <2 1.5 1.2 CRP <0.3 0.07 0.07

<Case 3> 58-year-old male Chief complaint: Total joint pain and edema of the left and fourth fingers Current history: Interferon due to chronic active hepatitis C from November 1990 to late June 1991 The therapy (Smiferon 600M-units x 56 times) was received. He had improved liver function, but was instructed to take a diet because of a decrease in pancreatic function. From mid-November 1992, pain and swelling of all joints of the fourth and fifth fingers of the left hand began to be recognized. As a result of a serum test, systemic lupus erythematosus was diagnosed, and the above composition of the present invention was administered at 6 tablets per day for 14 days for pain control. There were no concomitant medications. On the second day after administration of the composition of the present invention, the disappearance of pain was observed.
Since the swelling of the joint disappeared on the day, administration of the composition was stopped on the 6th day. Inspection result: Item normal value H4 / Nov / H5 / January RF <40 19.5 19.5 LE test (-) (-) (-) Antinuclear antibody <20 640 (homo) 160 (homo) anti-ss -DNA antibody <2 9.4 6.7 anti-ds-DNA antibody <2 0.9 0.9 CRP <0.3 0.06 0.17

<Case 4> 41-year-old woman Chief complaint: back muscle pain, back pain, both hand joint pain, both knee joint pain Current medical history: From around March 1991, he began orthopedic surgery at the National Hospital for ossification of the cervical posterior longitudinal ligament. He was consulted and treated. In May of the same year, she was diagnosed with low back pain and returned to the orthopedic surgery. She was diagnosed with a lumbar disc herniation. She received an antiphlogistic and a topical drug, but did not improve. 5, S.). However, back pain and pain in the lumbar surgery department did not decrease even after that. In July 1992, both hands and knee joint pain and general malaise were added. As a result, the patient was diagnosed with multiple rheumatoid arthritis. She was prescribed Kampo Shirei-to, but her pain did not improve, and she was prescribed only NM21 6 tablets per day from mid-October. As a result, an effect of lowering the rheumatoid factor (RF value) was obtained as described below. At the consultation two weeks later, the joint pain had completely disappeared. Inspection result: Item normal value H4 Oct. H4 Nov. H5 Jan. Jan. RF <40 54.3 57.5 42.4 LE test (-) (-) (-) (-) Antinuclear antibody <20 20 or less 20 or less 20 or less Anti-ss-DNA antibody <20.5 0.6 1.1 Anti-ds-DNA antibody <20.5 0.9 3.0 CRP <0.3 0.26 0.070 .06

<Toxicity test> Since the thymus is an internal organ of mammals and is also used as a cooking ingredient, thymic powder is not considered to be toxic. However, just in case, LD50 value which is one of acute toxicity tests Animal experiments for Twelve male ddy mice (average weight 23.9 g) and twelve females (average weight 21.6 g) were selected as experimental animals, and calf thymus freeze-dried powder was dissolved in water and orally administered using a gastric tube. Then, observation was performed in a rearing room at a room temperature of 23 ± 2 ° C. and a humidity of 50 ± 5%. The dose was 100 m / mouse for both male and female groups in terms of calf thymus freeze-dried powder.
g. After the calf thymus administration, the general condition of the experimental animals was observed daily. Fifteen days after the administration, all mice were sacrificed, necropsied and visually observed. As a result of observation for 14 days, no death cases were observed. Therefore, the LD50 value is 4.0 g or more per 1 kg of mouse body weight,
It was 240 g or more when converted to a human of 0 kg, which proved to be extremely safe. Oral administration of freeze-dried calf thymus powder did not change the behavior of the mice at all, and did not show any toxic symptoms.

[0019]

As described above, the pharmaceutical composition of the present invention has an antinuclear antibody reducing effect and a rheumatoid factor (RF) value reducing effect, has a drug effect on systemic lupus erythematosus and malignant rheumatism, and has no side effects. . Therefore, it can be used for pharmaceuticals and the like. In addition to systemic lupus erythematosus and malignant rheumatism, Behcet's disease,
It is presumed that it is also effective for scleroderma, dermatomyositis and polymyositis, idiopathic thrombocytopenic purpura, ulcerative colitis, and the like.

──────────────────────────────────────────────────続 き Continued on the front page (51) Int.Cl. ⁶ Identification code FI A61K 31/51 A61K 31/51 31/525 31/525 31/68 31/68 33/06 33/06 35/78 35/78 W (72) Inventor Katsumichi Matsushige 8-22-19 Miyamoto, Funabashi City, Chiba Prefecture (72) Inventor Yoshiaki Ishihama 1-35-13-203 Tobita Pay, Chofu City, Tokyo (72) Inventor Miyazawa Kaori 2882-52 Kanaicho, Machida-shi, Tokyo (56) References JP-A-6-107553 (JP, A) (58) Fields investigated (Int. Cl. ⁶ , DB name) A61K 35/24

Claims (13)

(57) [Claims] 1. A pharmaceutical composition for reducing an antinuclear antibody comprising a thymus of a mammal as a main component. 2. A pharmaceutical composition for reducing rheumatoid factor comprising a thymus of a mammal as a main component. 3. A pharmaceutical composition for reducing antinuclear antibodies, comprising a thymus of a mammal as a main component, and further comprising one or more of the following components. Barley extract, Sansho extract, Goka bark extract, Matsuba extract, Licorice extract 4. A pharmaceutical composition for reducing rheumatoid factor, comprising a thymus of a mammal as a main component and further comprising one or more of the following components. Barley extract, Sansho extract, Goka bark extract, Matsuba extract, Licorice extract 5. A pharmaceutical composition for reducing antinuclear antibodies, comprising a thymus of a mammal as a main component, and further comprising at least one or more components of each of the following groups 1 and 2. Group 1: Barley extract, Sansho extract, Gokaku extract, Matsuba extract, Licorice extract Group 2: Fragrance extract, Chicken blood wort extract, Keishi extract,
Safflower extract, kaikei ground yellow stem tea powder 6. A pharmaceutical composition for reducing rheumatoid factor, comprising a thymus of a mammal as a main component, and further comprising at least one or more components of each of the following groups 1 and 2. Group 1: Barley extract, Sansho extract, Gokaku extract, Matsuba extract, Licorice extract Group 2: Fragrance extract, Chicken blood wort extract, Keishi extract,
Safflower extract, kaikei ground yellow stem tea powder 7. A pharmaceutical composition for reducing an antinuclear antibody, comprising a thymus of a mammal as a main component, and at least one or more components of each of the following groups 1, 2 and 3: Stuff. Group 1: Barley extract, Sansho extract, Gokaku extract, Matsuba extract, Licorice extract Group 2: Fragrance extract, Chicken blood wort extract, Keishi extract,
Safflower extract, Huaiqing yellow twig tea powder Group 3: Calcium, B vitamins, Vitamin E 8. A pharmaceutical composition for reducing rheumatoid factor, comprising a thymus of a mammal as a main component and at least one or more components of each of the following groups 1, 2 and 3: . Group 1: Barley extract, Sansho extract, Gokaku extract, Matsuba extract, Licorice extract Group 2: Fragrance extract, Chicken blood wort extract, Keishi extract,
Safflower extract, Huaiqing yellow twig tea powder Group 3: Calcium, B vitamins, Vitamin E 9. A pharmaceutical composition for reducing antinuclear antibodies, comprising the following components in the following ranges: 3. The thymus end of mammals: 10 wt% or more and 40 wt% or less Adlay extract: 6 wt% or more and 24 wt% or less Sansho extract: 1.2 wt% or more and 4.8 wt% or less Pokada extract: 5 wt% or more and 20 wt% or less Matsuba extract: 4. 0 wt% or more and 16.0 wt% or less Licorice extract: 2.3 wt% or more and 9.2 wt% or less Fragrant extract: 2.5 wt% or more and 10.0 wt% or less Chicken blood wister extract: 5 wt% or more and 20 wt% or less Keishi extract: 2.5 wt% or more and 10 wt% or less Safflower extract: 2.5 wt% or more and 10 wt% or less Kaikei ground yellow stalk tea powder: 4.7 wt% or more and 19.0 wt% or less Calcium: 0.6 wt% or more and 2.7 wt% or less Thiamine nitrate (Vitamin B1): 1.7 wt% or more and 6.8 wt% or less Riboflavin (vitamin B2): 3.4 w % To 13.6% by weight Pyridoxine hydrochloride (vitamin B6): 3.4% by weight to 13.6% by weight cyanocobalamin (vitamin B12): 0.00003% by weight to 0.00012% by weight Tocopherol (vitamin E): 1. 4 wt% or more and 5.6 wt% or less 10. A pharmaceutical composition for reducing rheumatoid factor, comprising the following components in the following range: 3. Thymus end of mammals: 10 wt% or more and 40 wt% or less Adlay extract: 6 wt% or more and 24 wt% or less Sansho extract: 1.2 wt% or more and 4.8 wt% or less Phosphorus extract: 5 wt% or more and 20 wt% or less Matsuba extract: 4. 0 wt% or more and 16.0 wt% or less Licorice extract: 2.3 wt% or more and 9.2 wt% or less Fragrant extract: 2.5 wt% or more and 10.0 wt% or less Chicken blood wister extract: 5 wt% or more and 20 wt% or less Keishi extract: 2.5 wt% or more and 10 wt% or less Safflower extract: 2.5 wt% or more and 10 wt% or less Kaikei ground yellow stalk tea powder: 4.7 wt% or more and 19.0 wt% or less Calcium: 0.6 wt% or more and 2.7 wt% or less Thiamine nitrate (Vitamin B1): 1.7 wt% or more and 6.8 wt% or less Riboflavin (vitamin B2): 3.4 w % To 13.6% by weight Pyridoxine hydrochloride (vitamin B6): 3.4% by weight to 13.6% by weight cyanocobalamin (vitamin B12): 0.00003% by weight to 0.00012% by weight Tocopherol (vitamin E): 1. 4 wt% or more and 5.6 wt% or less 11. The pharmaceutical composition for reducing an antinuclear antibody according to claim 1 or 3 or 5 or 7 or 9, or the rheumatoid factor according to claim 2 or 4 or 6 or 8 or 10. Pharmaceutical compositions for reduction. 12. The pharmaceutical composition for reducing an antinuclear antibody according to claim 1 or 3 or 5 or 7 or 9, or the rheumatoid factor according to claim 2 or 4 or 6 or 8 or 10. Pharmaceutical compositions for reduction. 13. The pharmaceutical composition for reducing an antinuclear antibody according to claim 1, wherein the mammal is a pig, or the rheumatism according to claim 2, 4 or 6, or 8 or 10. Pharmaceutical compositions for factor reduction.