KR870000237B1 - Stabilization methods of serrapeptase - Google Patents

Stabilization methods of serrapeptase Download PDF

Info

Publication number
KR870000237B1
KR870000237B1 KR8205845A KR820005845A KR870000237B1 KR 870000237 B1 KR870000237 B1 KR 870000237B1 KR 8205845 A KR8205845 A KR 8205845A KR 820005845 A KR820005845 A KR 820005845A KR 870000237 B1 KR870000237 B1 KR 870000237B1
Authority
KR
South Korea
Prior art keywords
serapeptase
lactose
suspension
added
solution
Prior art date
Application number
KR8205845A
Other languages
Korean (ko)
Other versions
KR840002901A (en
Inventor
사까시 이께다
쇼이찌 나가히로
Original Assignee
구라바야시 이꾸시로
다께다야꾸힝 고오교 가부시끼가이샤
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by 구라바야시 이꾸시로, 다께다야꾸힝 고오교 가부시끼가이샤 filed Critical 구라바야시 이꾸시로
Publication of KR840002901A publication Critical patent/KR840002901A/en
Application granted granted Critical
Publication of KR870000237B1 publication Critical patent/KR870000237B1/en

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N9/00—Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
    • C12N9/98—Preparation of granular or free-flowing enzyme compositions
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N9/00—Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N9/00—Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
    • C12N9/14—Hydrolases (3)
    • C12N9/48—Hydrolases (3) acting on peptide bonds (3.4)
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N9/00—Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
    • C12N9/14—Hydrolases (3)
    • C12N9/48—Hydrolases (3) acting on peptide bonds (3.4)
    • C12N9/50—Proteinases, e.g. Endopeptidases (3.4.21-3.4.25)
    • C12N9/52—Proteinases, e.g. Endopeptidases (3.4.21-3.4.25) derived from bacteria or Archaea
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N9/00—Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
    • C12N9/96—Stabilising an enzyme by forming an adduct or a composition; Forming enzyme conjugates

Landscapes

  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Genetics & Genomics (AREA)
  • Organic Chemistry (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Zoology (AREA)
  • Wood Science & Technology (AREA)
  • Molecular Biology (AREA)
  • Microbiology (AREA)
  • Biotechnology (AREA)
  • Biomedical Technology (AREA)
  • Biochemistry (AREA)
  • General Engineering & Computer Science (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Enzymes And Modification Thereof (AREA)
  • Medicinal Preparation (AREA)

Abstract

Stabilized lyophilised powders contg. serrapeptase (I), lactose(II), sucrose, gelatin, or aspartic or glutamic acid were prepd. Thus, a 15% (wet./vol.) aq. soln. of II (30-150g) was added to a 10% (wt./ vol.) aq. soln. of I (100g), and the mixt. was lyophilized under condns. of initial temp. of -55≰C, initial pressue of 10-3mmHg, final temp. after 27h of 60≰C, and final pressure of 10-1mmHg. 5mg lyophilized mixt. was blended with lactose 87, corn starch 37.5, iso- Pro 0.015, and Mg-stearate 0.5mg, crushed, dried, and the granule size was adjusted. The mixts. were compressed to give tablets each weighing 130mg.

Description

세라펩타제를 안정화 시키는 방법How to stabilize serapeptase

본 발명은 안정화 된 세라펩타제를 함유하는 분말 조성물을 생성하는 방법에 관한 것이다.The present invention relates to a method for producing a powder composition containing stabilized serapeptase.

세라펩타제는 배양배지에서 예를 들어 세라티아(Serratia) sp. E15을 배양함으로써 생성할 수 있는 효소이며 소염작용을 가지고 있다.Serrapeptase is described, for example, in Serratia sp. It is an enzyme that can be produced by culturing E 15 and has an anti-inflammatory effect.

세라펩타제는 버교적 열에 민감하며 불리하게도 산업적 규모에 있어서 분말 형태로 제조시 동결 건조의 단계에서 효소활성을 잃는다.Cerapeptase is sensitive to thermal heat and adversely loses enzymatic activity at the stage of lyophilization when prepared in powder form on an industrial scale.

상기와 같은 관점에서, 본 발명자들은 분말형태의 효소적으로 안정화된 세라펩타제를 제조하기 위해 노력하였다. 그 결과로서 본 발명자들은 세라펩타제의 효소 활성은 락토오즈, 슈크로오즈, 젤라틴, 아스파르트산 또는 그의 염 그리고 글루탐산 또는 그의 염중 하나 이상을 세라펩타제를 함유한 용액에 액상에서 첨가하여 생성된 혼합물이 동결 건조 되었을때 안정화 될 수 있다.In view of the above, the present inventors have tried to prepare enzymatically stabilized serapeptase in powder form. As a result, the inventors have found that the enzymatic activity of serapeptase is a mixture produced by adding at least one of lactose, sucrose, gelatin, aspartic acid or a salt thereof and glutamic acid or a salt thereof to a solution containing serapeptase in a liquid phase. This can be stabilized when lyophilized.

이 발견을 기초로 하여 더 많은 연구를 행한 결과 본 발명을 완성하게 되었다.Based on this finding, further research has led to the completion of the present invention.

본 명세서에서 락토오즈, 슈크로오즈, 젤라틴, 아스파르트산 또는 그 염과 글루탐산 또는 그 염중의 하나이상이 때때로 본첨가제로써 이용된다.Herein, one or more of lactose, sucrose, gelatin, aspartic acid or salts thereof and glutamic acid or salts thereof are sometimes used as the main additive.

본 발명은 락토오즈, 슈크로오즈, 젤라틴, 아스파르트산 또는 그 염과 글루탐산 또는 그 염 중의 하나 이상을 세라펩타제 함유 용액 또는 헌탁액에 첨가하여 생성된 용액 또는 현탁액을 동결 건조시킨 안정화 세라펩타제를 함유하는 분말 조성물을 제조하는 방법에 관한 것이다.The present invention relates to a stabilized serapeptase wherein a solution or suspension produced by adding lactose, sucrose, gelatin, aspartic acid or salts thereof and glutamic acid or salts thereof to a serapeptase containing solution or suspension is lyophilized. It relates to a method for producing a powder composition containing.

뿐만 아니라, 본 발명은 본 첨가제를 세라펩타제 함유 용액 또는 현탁액에 첨가한 후 생성된 용액 또는 현탁액을 동결건조 하여 제조한 안정화 세라펩타제를 함유한 조성물에 관한 것과 본 첨가제를 세라펩타제 함유 용액 또는 현탁액에 첨가한 후 생성된 용액 또는 현탁액을 동결 건조시킨 세라펩타제를 안정화시키는 방법에 관한 것아다.In addition, the present invention relates to a composition containing a stabilized serapeptase prepared by adding the present additive to a serapeptase-containing solution or suspension, and then lyophilizing the resulting solution or suspension, and the additive containing the serapeptase-containing solution. Or to a method for stabilizing serapeptase from which the resulting solution or suspension is freeze-dried after addition to the suspension.

세라펩타제는 예를 들면 배양배지에서 세라티아 sp. E15을 배양함으로써 생성될 수 있다. [Cf. 미국특허공고 번호 3,691, 014] 상기의 세라티아 sp. E15는 기탁번호 ATCC 21074로 아메리칸 타입 컬처 콜렉션(American Type Culture Collection)에 1967년 5월 15일에 기탁되었으며 균주 I의 아메리칸 타입 컬처 콜렉션 카탈로그 14권 1980과 15권 1982에 기록되었다.Serrapeptase is, for example, in Seratia sp. Can be produced by culturing E 15 . [Cf. United States Patent Publication No. 3,691, 014] The Seratia sp. E 15 was deposited in the American Type Culture Collection on May 15, 1967 under accession number ATCC 21074 and recorded in strain I American Type Culture Collection Catalog 14, 1980 and 15, 1982.

세라펩타제 함유 용액은 예를 들면 아세톤이나 저급알콜(메틸알콜, 에릴알콜, 이소프로필알콜)과 같은 유기 용제를 함유한 수용액이다.The cerapeptase-containing solution is an aqueous solution containing an organic solvent such as acetone or lower alcohol (methyl alcohol, aryl alcohol, isopropyl alcohol), for example.

상기 용액의 제조를 위해서 미국특허 공고번호 3,691,014의 방법에 따라 세라터아 sp. E15를 배양함으로써 생성된 것을 동결건조 하기전 프로테아제 함유 용액이나 상기 방법에 의해 생성된 것을 한번 동결건조한 생성물을 이용한다.For the preparation of the solution according to the method of US Patent Publication No. 3,691,014 Serratera sp. The protease-containing solution or the product lyophilized once produced by the above method is used before lyophilization of the product produced by culturing E 15 .

상기 용액에서 세라펩타제 농도는 효소의 역가가 약 5,000PU/mg(PU에 대해서는 미국특허 1 3,691,014를 참고할 것)이라고 가정하여 약 50∼200mg/ml가 바람직하다.The serapeptase concentration in the solution is preferably about 50 to 200 mg / ml assuming that the enzyme titer is about 5,000 PU / mg (refer to US Pat. No. 3,691,014 for PU).

상기 용액의 pH는 6.5∼7.5가 바람직하다.The pH of the solution is preferably 6.5 to 7.5.

아스파르트산의 염은 예를들면 포타슘 아스파테이트, 소듐 아스파 테미트, 칼슘아스파테이트가 있다. 글루탐산의 염은 포타슘 클루타메이트, 소듐 글루타메이트, 칼슘 글루타메이트가 있다.Salts of aspartic acid are, for example, potassium aspartate, sodium aspartate, calcium aspartate. Salts of glutamic acid include potassium glutamate, sodium glutamate, calcium glutamate.

본 첨가제에서 락토오즈는 가장 바람직하다.Lactose is most preferred in this additive.

본 첨가제를 세라펩타제 함유 용액에 첨가하는데 있어, 본 첨가제는 아세톤이나 알콜(메틸알콜, 에틸알콜)을 함유한 수용액의 물에 용해되거나 현탁되며, 그 용액 또는 현탁액은 상기에 서술된 세라펩타제 함유용액에 첨가된다. 첨가후 생성된 혼합물은 용액 또는 현탁액일 것이다. 본 첨가제는 세라펩타제 중량부당 약 0.5∼1.5중량부의 양으로 사용하는 것이 적당하다. 동결건조 직전의 용액 또는 현탁액에서 세라펩타제 농도는효소 역가가 약 5,000PU/mg이라고 가정하여 약 70∼150mg/ml가 적당하다.In adding the present additive to a serapeptase containing solution, the additive is dissolved or suspended in water in an aqueous solution containing acetone or alcohol (methyl alcohol, ethyl alcohol), the solution or suspension of which is described above. It is added to the containing solution. The resulting mixture after addition will be a solution or suspension. The additive is suitably used in an amount of about 0.5 to 1.5 parts by weight per weight part of serapeptase. The serapeptase concentration in the solution or suspension immediately before lyophilization is about 70-150 mg / ml, assuming that the enzyme titer is about 5,000 PU / mg.

이 발명을 실시함에 있어 동결건조는 어떤 특별한 제한 없이 통상적인 조건하에 수행된다. 그러므로 예를들면 동결건조 온도는 약 -60℃ 내지 +60℃의 범위 안에서, 압력은 10-3내지 10-1mmHg의 범위 안에서, 시간은 24 내지 36시간의 범위 안에서 적당히 선택될 수 있다.In carrying out this invention, lyophilization is carried out under conventional conditions without any particular limitation. Thus, for example, the lyophilization temperature may be appropriately selected in the range of about -60 ° C to + 60 ° C, the pressure in the range of 10 -3 to 10 -1 mmHg, and the time in the range of 24 to 36 hours.

이와같이 수득된 분말 조성물은 매우 안정화된 효소활성을 가진 세라펩타제를 함유한다. 상기의 조성물은 분말형이나 무정형으로 있으며 실질적 손실 없이 효소활성을 유지하며, 정제제조에 사용될 경우 효소활성이 상당히 유지된 정제를 얻을 수 있다. 그러므로 본 방법은 산업적 규모로 세라펩타제의 안정화된 효소 조성물을 제조하는데 이용될 수 있다.The powder composition thus obtained contains cerapeptase with very stabilized enzymatic activity. The composition is in the form of powder or amorphous, and maintains enzymatic activity without substantial loss, and when used in the manufacture of tablets, it is possible to obtain a tablet in which the enzymatic activity is significantly maintained. The method can therefore be used to prepare stabilized enzyme compositions of serapeptase on an industrial scale.

하기의 실시예는 본 발명을 더 구체적으로 설명하고 있으나 본 발명이 이에 한정되는 것은 아니다. 사용된 효소는 약 5,000PU/mg의 역가를 가지고 있다.The following examples further illustrate the present invention, but the present invention is not limited thereto. The enzyme used has a titer of about 5,000 PU / mg.

[실시예 1]Example 1

락토오즈 15w/v% 수용액은 하기의 표에 따라 세라펩타제 10w/v% 수용액에 첨가되며, 각 혼합물은 초기온도 -55℃, 초기압력 10-3mmHg 27시간후 최종온도 +60℃, 최종압력 10-1mmHg의 조건하에 동결건조 된다.Aqueous lactose 15w / v% aqueous solution is added to 10w / v% aqueous solution of serapeptase according to the following table, and each mixture has initial temperature of -55 ° C, initial pressure of 10 -3 mmHg, final temperature of + 60 ° C after 27 hours, final Lyophilized under conditions of pressure 10 −1 mmHg.

Figure kpo00001
Figure kpo00001

각 동결건조 생성물에 대하여 효소활성을 분석한다. 결과는 하기의 표와 같다.Enzyme activity is analyzed for each lyophilized product. The results are shown in the table below.

Figure kpo00002
Figure kpo00002

본 발명에 의해 동결 건조된 효소 생성물은 안정하다.The lyophilized enzyme product according to the invention is stable.

[정제제조][Tablet manufacturing]

본 발명에 따라 생성된 세라펩타제는 하기의 표에 따라 혼련 및 건조한 후 과립크기를 조정하여 1.3톤/㎠의 압력에서 7mm

Figure kpo00003
, 5R 막자(pestle)를 사용하여 정제 제조하며 각 정제의 중량은 130mg으로 한다.The serapeptase produced according to the present invention was kneaded and dried according to the following table to adjust the granule size to 7 mm at a pressure of 1.3 ton / cm 2.
Figure kpo00003
Tablets were prepared using 5R pestle, and the weight of each tablet was 130 mg.

Figure kpo00004
Figure kpo00004

[실시예 2]Example 2

락토오즈 10w/v% 수용액은 하기에 표시된 것과 같이 7.5w/v%의 세라펩타제와 5w/v%의 아세톤을 함유한 수용액에 혼합하며 혼합물은 초기 온도 -55℃, 초기 압력 10-3mmHg, 27시간 후 최종 온도 +60℃, 최종 압력 10-1mmHg에서 동결건조시킨다.Aqueous lactose 10w / v% solution is mixed into an aqueous solution containing 7.5w / v% cerapeptase and 5w / v% acetone as indicated below, and the mixture is at an initial temperature of -55 ° C and an initial pressure of 10 -3 mmHg. After 27 hours, lyophilize at a final temperature of + 60 ° C. and a final pressure of 10 −1 mmHg.

Figure kpo00005
Figure kpo00005

동결건조 생성물에 대하여 효소활성을 분석한다. 결과는 하기의 표와 같다.The enzyme activity is analyzed for the lyophilized product. The results are shown in the table below.

Figure kpo00006
Figure kpo00006

1)∼4)의 잔류역가 %는 실시예 1과 같다.The residual titers% of 1) to 4) are the same as in Example 1.

본 발명에 의해 동결건조된 효소 생성물은 안정하다.The lyophilized enzyme product according to the invention is stable.

[실시예 3]Example 3

락토오즈 15w/v% 수용액이나 하기 표에 명시된 물질은 하기에 표시된 것과 같이 세라펩타제 10w/v% 수용액과 혼합하며 혼합물은 초기온도 -55℃, 초기압력 10-3mmHg, 27시간 후 최종온도 +60℃, 최종압력 10-1nmHg에서 동결건조시킨다.15 w / v% aqueous solution of lactose or the substances specified in the table below are mixed with 10 w / v% aqueous solution of cerapeptase as indicated below, and the mixture is at an initial temperature of −55 ° C., an initial pressure of 10 −3 mmHg, and a final temperature after 27 hours. Lyophilize at + 60 ° C., final pressure 10 −1 nmHg.

Figure kpo00007
Figure kpo00007

동결 건조 생성물에 대해 효소활성을 분석한다. 결과는 하기의 표와 같다.Enzyme activity is analyzed for lyophilized products. The results are shown in the table below.

Figure kpo00008
Figure kpo00008

1)∼4)의 잔류역가 %는 실시예 1과 같다.The residual titers% of 1) to 4) are the same as in Example 1.

본 발명에 의해 동결 건조된 효소생성물은 안정하다.The lyophilized enzyme product according to the invention is stable.

Claims (9)

락토오즈, 슈크로오즈, 젤라틴, 아스파르트산 또는 그 염, 글루탐산 또는 그 염 중의 하나 이상을 세라펩타제 함유용액 또는 현탁액에 첨가하여 생성된 용액 또는 현탁액을 동결건조시커는 것을 특징으로 하는 안정화된 세라펩타제를 함유한 분말 조성물의 제조방법.Stabilized Cera characterized by adding a lactose, sucrose, gelatin, aspartic acid or salts thereof, glutamic acid or salts thereof to a serapeptase containing solution or suspension to lyophilize the resulting solution or suspension. Method for producing a powder composition containing peptase. 제1항에 있어서, 락토오즈가 세라펩타제 함유 용액 또는 현탁액에 첨가됨을 특징으로 하는 방법.The method of claim 1, wherein lactose is added to the serapeptase containing solution or suspension. 제2항에 있어서, 락토오즈가 세라펩타제 중량의 0.5∼1.5배의 양으로 첨가됨을 특징으로 하는 방법.The method of claim 2, wherein the lactose is added in an amount of 0.5 to 1.5 times the weight of the serapeptase. 락토오즈, 슈크로오즈, 젤라틴, 아스파르트산 또는 그염, 글루탐산 또는 그 염 중의 하나 이상을 세라펩타제 함유 용액 또는 현탁액에 첨가하여 생성된 용액 또는 현탁액을 동결건조하여 생성된 안정화된 세라펩타제를 함유하는 조성물.Contain a stabilized serapeptase produced by lyophilizing the resulting solution or suspension by adding one or more of lactose, sucrose, gelatin, aspartic acid or salts thereof, glutamic acid or salts thereof to the serapeptase containing solution or suspension Composition. 제4항에 있어서, 락토오즈가 세라펩타제 함유 용액 또는 현탁액에 첨가됨을 특징으로 하는 조성물.5. The composition of claim 4, wherein lactose is added to the serapeptase containing solution or suspension. 제5항에 있어서, 락토오즈가 세라펩타제 중량의 0.5∼1.5배의 양으로 첨가됨을 특징으로 하는 조성물.6. The composition of claim 5, wherein the lactose is added in an amount of 0.5 to 1.5 times the weight of the cerapeptase. 락토오즈, 슈크로오즈, 젤라틴, 아스파르트산 또는 그 염, 글루탐산 또는 그 염을 세라펩타제 함유 용액 또는 현탁액에 첨가하여 생성된 용액 또는 현탁액을 동결건조시키는 것을 특징으로 하여 세라펩타제를 안정화시키는 방법.Lactose, sucrose, gelatin, aspartic acid or salts thereof, glutamic acid or salts thereof are added to a serapeptase-containing solution or suspension to lyophilize the resulting solution or suspension, thereby stabilizing serapeptase. . 제7항에 있어서, 락토오즈가 세라펩타제 함유 용액 또는 현탁액에 첨가됨을 특징으로 하는 방법.8. The method of claim 7, wherein lactose is added to the serapeptase containing solution or suspension. 제8항에 있어서, 락토오즈가 세라펩타제 중량의 0.5∼1.5배의 양으로 첨가됨을 특징으로 하는 방법.9. The method of claim 8, wherein the lactose is added in an amount of 0.5-1.5 times the weight of the serapeptase.
KR8205845A 1981-12-28 1982-12-28 Stabilization methods of serrapeptase KR870000237B1 (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
JP56215724A JPS58134991A (en) 1981-12-28 1981-12-28 Stabilization of serratiopeptidase
JP215724 1981-12-28

Publications (2)

Publication Number Publication Date
KR840002901A KR840002901A (en) 1984-07-21
KR870000237B1 true KR870000237B1 (en) 1987-02-18

Family

ID=16677126

Family Applications (1)

Application Number Title Priority Date Filing Date
KR8205845A KR870000237B1 (en) 1981-12-28 1982-12-28 Stabilization methods of serrapeptase

Country Status (7)

Country Link
JP (1) JPS58134991A (en)
KR (1) KR870000237B1 (en)
ES (1) ES8405841A1 (en)
FR (1) FR2519021B1 (en)
GR (1) GR78417B (en)
IT (1) IT1157994B (en)
PT (1) PT76042B (en)

Families Citing this family (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CA1230300A (en) * 1983-06-06 1987-12-15 Michael K. Hoskins Stabilized isoenzyme control product
US5405767A (en) * 1992-04-08 1995-04-11 Solvay Enzymes, Inc. Purified enzyme concentrate and method of preparation
US6288030B1 (en) * 1993-12-22 2001-09-11 Amgen Inc. Stem cell factor formulations and methods
DE69523163T2 (en) * 1994-07-20 2002-03-07 Kyowa Hakko Kogyo Kk METHOD FOR PRODUCING STABILIZED DRIED CARBOXYESTERASE
CU23475A1 (en) 2004-07-08 2009-12-17 Ct Ingenieria Genetica Biotech PHARMACEUTICAL COMPOSITION CONTAINING SERRALISINE POLYPEPTIDE FRAGMENTS
KR100667852B1 (en) 2006-01-13 2007-01-11 삼성전자주식회사 Apparatus and method for eliminating noise in portable recorder
WO2017111569A1 (en) * 2015-12-21 2017-06-29 Clinica De Avances Oculares, S.A.P.I. De C.V. Pharmaceutical combination and formulation for the treatment of eye diseases
CN108309941B (en) * 2018-03-20 2023-08-11 南京工业大学 Serratase external powder and preparation method thereof

Family Cites Families (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
FR1352103A (en) * 1960-02-26 1964-02-14 Process for stabilizing sensitive or unstable enzymes, especially catalase
FR1533993A (en) * 1967-06-13 1968-07-26 Takeda Chemical Industries Ltd Process for preparing a protease
JPS5534001A (en) * 1978-08-28 1980-03-10 Noda Sangyo Kagaku Kenkyusho Stabilization of sarcosine oxidase
FR2444465A1 (en) * 1978-12-22 1980-07-18 Green Cross Corp Antithrombotic agent contg. urokinase - produced by maintaining pH neutral or weakly alkaline during each processing step for urokinase prodn.

Also Published As

Publication number Publication date
PT76042B (en) 1986-01-27
FR2519021B1 (en) 1985-07-26
IT1157994B (en) 1987-02-18
FR2519021A1 (en) 1983-07-01
IT8268523A0 (en) 1982-12-27
ES518579A0 (en) 1984-06-16
PT76042A (en) 1983-01-01
JPS58134991A (en) 1983-08-11
GR78417B (en) 1984-09-27
ES8405841A1 (en) 1984-06-16
JPH0218069B2 (en) 1990-04-24
KR840002901A (en) 1984-07-21

Similar Documents

Publication Publication Date Title
US4266031A (en) Protease product of reduced allergenicity
FI61807B (en) FOERFARANDE FOER STABILIZERING AV MENINGOKOCKPOLYSACKARID
AU718901B2 (en) Stabilized albumin-free recombinant factor VIII preparation having a low sugar content
US3515642A (en) Method for preparing a stabilized enzyme composition
KR870000237B1 (en) Stabilization methods of serrapeptase
KR100370257B1 (en) Compressible Enzyme Powder
HU200101B (en) Process for producing stabilized pharmaceutical compositions containing human tissue plasminogene activator
US4315002A (en) Solid pharmaceutical or diagnostic agent containing dextran and its preparation
CN113694189A (en) Freeze-drying protective agent for protease K and preparation method thereof
JPS5849160B2 (en) Process for producing N-acyl-L-methionine
Uchida et al. Fermentative production of hypoxanthine derivatives
JPH0411194B2 (en)
US3523871A (en) Stabilization of catalase
EP0386668A2 (en) Lyophilized dihydrochloride of 7-[alpha-(2-aminothiazol-4-yl)-alpha-(Z)-methoxyiminoacetamido)-3-[(1-methyl-1-pyrrolidinium)-methyl]-3-cephem-4-carboxylate
EP1053232B1 (en) Process for the preparation of sotolon
Fadnavis et al. Peptide synthesis mediated by immobilized and viable baker's yeast in reverse micelles: synthesis of leucine enkephalin analogues
RU2160992C1 (en) Dry biopreparation and method of its preparing
JPH0452252B2 (en)
RU2169574C1 (en) Method of biopreparation preparing and dry biopreparation
RU2118363C1 (en) Microbiological medium for growing and diagnosis of bacteria of genus listeria
US3792160A (en) Method of treating inflammation and composition therefor
GB2024830A (en) Protease Product of Reduced Allergenicity
US5376678A (en) Active principle based on avermectins, related strain and process for the preparation thereof, as well as veterinary compositions containing it
KR970004014B1 (en) Enhanced preparing method of l-tryptophan by tryptophanase using glycerol
Kim et al. Immobilized arylsulfotransferase

Legal Events

Date Code Title Description
G160 Decision to publish patent application
O035 Opposition [patent]: request for opposition

Free format text: OPPOSITION NUMBER: 001987000705; OPPOSITION DATE: 19870417

J2X1 Appeal (before the patent court)

Free format text: TRIAL NUMBER: 1988201000333; APPEAL AGAINST DECISION TO DECLINE REFUSAL